PubMed Health⌕ Search

Biomedical subjects

T Löning

Publications and source records attributed to T Löning.

At least 37 records · Page 2Linked to original sources
PubMed2001

Alterations of INK4a(p16-p14ARF)/INK4b(p15) expression and telomerase activation in meningioma progression.

Dysregulation of cell cycle progression and telomerase activation have been implicated in malignant tumor progression as well as in the evasion of senescence and immortalization. We have investigated expression of the cell cycle control and tumor suppressor genes INK4a(p16-p14ARF), INK4b(p15-p10) and RB, and their relation to telomerase activation during malignant meningioma progression. 7/26 (27%) benign, 3/12 (25%) atypical but 4/7 (57%) anaplastic tumors lacked both, p16 and p15 protein expression. 14/39 (36%) benign and atypical but 5/7 (71%) anaplastic meningiomas contained no p14ARF mRNA. 2/46 (4%) tumors failed to express pRB. We observed frequent differential loss of expression of the alternatively spliced INK4a tumor suppressors p16 and p14ARF. Exclusive expression of the alternative INK4b transcript p10 possibly at the expense of p15 and therefore resulting in loss of p15 tumor suppressor activity was noted in two meningiomas. We have previously described telomerase activity or expression of the telomerase catalytic subunit hTERT in this meningioma series. Telomerase activation was detected in 10/27 (37%) benign, but 18/19 (95%) non-benign meningiomas. We observed no significant overall correlation between loss of INK4a/INK4b expression and telomerase activation. In conclusion, our results suggest a greater role for losses of INK4a/INK4b gene products in meningioma formation and malignant progression than previously thought. Inactivation of p16/p15- and pl4ARF-dependent pathways possibly in conjunction with telomerase activation might be critical steps for a meningioma cell towards escape from senescence, that is, immortalization.

Adult↗
PubMed2001

[About the prognostic value of Her-2 gene-amplification and cell-proliferation in salivary duct carcinoma of the major salivary glands - a pilot-study].

INTRODUCTION: The salivary duct carcinoma (sdc) represents a rare variant of the group of adeno-carcinomas of the salivary glands. Histopathologically, it is marked by solid and cribriform cell nests with central necrosis, displaying distinct similarity with the ductal carcinoma of the breast, where prognosis can be correlated with Her-2 gene-amplification. Based on this histopathological similarity, the prognostic value of Her-2 gene amplification in SDC was examined in the presented pilot-study. PATIENTS AND METHODS: Four own patients with different clinical courses were examined in regard to their histopathological features, Her-2 gene-amplification and proliferation (Ki67). RESULTS: Three of the four patients died tumor related 2.4, 5.5 and 8.2 years after initial diagnosis. The remaining patient died tumor-free 6 year after diagnosis (myocardial infarct). The two patients with an early recurrent disease and distant metastasis showed a high Her-2 expression and proliferation (Ki67), compared to the other two patients. CONCLUSION: In the presented pilot-study a distinct correlation between Her2-gene-amplification, proliferation (Ki67) and clinical course could be observed. Additional analysis to evaluate this aspect seems rectified, especially under recognition of therapy decisions.

Adenocarcinoma↗
PubMed2001

Expression pattern of the adhesion molecule CEACAM1 (C-CAM, CD66a, BGP) in gestational trophoblastic lesions.

CEACAM1 (CD66a, BGP, C-CAM) is an adhesion molecule of the carcinoembryonic antigen (CEA) family which has been shown to be normally expressed at the apical pole of epithelial cells and to show a dysregulated expression pattern in tumors derived from the latter. The purpose of the present study was to investigate the expression pattern of CEACAM1 in gestational trophoblastic lesions and to compare this expression with the one observed in the normal trophoblast. For this purpose, we performed immunohistochemistry using the 4D1/C2 monoclonal antibody which specifically recognizes CEACAM1 and does not interact with other members of the CEA family. Immunohistochemistry was performed on a total of 20 cases of gestational trophoblastic lesions including complete hydatidiform moles, one placental site trophoblastic nodule (PSN), one placental site trophoblastic tumor (PSTT), and three choriocarcinomas. Immunostaining for cytokeratin, hPL, hCG, and Ki-67 was also performed. Normal placental samples served as a control. CEACAM1 was absent from villous cyto- and syncytiotrophoblast in both normal placenta and hydatidiform molar samples. It was present in the benign extravillous trophoblast, with stronger expression in the proximal extravillous trophoblast of anchoring villi, but was also observed in interstitial and endovascular intermediate trophoblast and chorionic intermediate-like trophoblast. Partial expression was observed in the trophoblast proliferating from the surface of molar villi. In choriocarcinomas, areas of weak expression could be observed along with large areas without CEACAM1 expression. In the PSN and especially in the PSTT, CEACAM1 expression was stronger and more diffuse. The specific localization to extravillous trophoblast and its expression pattern in gestational trophoblastic lesions indicate that CEACAM1 can potentially be a helpful additional diagnostic marker in the differential diagnosis of such lesions.

Antigens, CD↗
PubMed2001

Relationship between telomerase activation and HPV 16/18 oncogene expression in squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix.

SILs (squamous intraepithelial lesions) comprise a wide spectrum of clinically and biologically heterogeneous lesions ranging from benign proliferations to precancerous lesions. Telomerase activation plays a critical role in cellular immortalization and might be important for malignant progression. The viral oncogenes E6 and E7 are the principal transforming genes of high-risk HPVs and are important in HPV-associated immortalization and neoplastic transformation. In this study we investigated the relationship between telomerase activity, telomerase RNA, and HPV 16/18 oncogene expression in low- and high-grade SILs and SCCs (squamous cell carcinomas) of the cervix uteri. Telomerase activity was examined by the TRAP-assay and expression of the telomerase RNA (hTR) and HPV 16/18 E6/E7 oncogenes by RNA/RNA-in situ hybridization (ISH). The associated HPV-type was determined by PCR. Telomerase activity was observed in 25/29 (86%) SCCs, 31/41 (76%) high-grade SILs, 6/14 (43%) low-grade SILs, and 1/28 (3.6%) normal cervical tissues. Expression of hTR and viral oncogenes increased significantly with histopathologic severity of the lesion (p < 0.0001). A correlation was found between telomerase activity and intensity of viral oncogene expression. These findings suggest that telomerase activation occurs early in cervical carcinogenesis and is predominantly found in high-grade SILs and cervical SCCs. Our findings support current experimental data that suggest that telomerase is at least partially activated by viral oncogenes of high-risk HPV types. Telomerase activity with concomitant strong viral oncogene expression might therefore characterize a subset of lesions that are at risk for malignant progression.

Carcinoma, Squamous Cell↗
PubMed2001

PTEN expression in breast and endometrial cancer: correlations with steroid hormone receptor status.

OBJECTIVE: The PTEN (MMAC1/TEP1) tumor suppressor gene is frequently mutated and homozygously deleted in human neoplasms, but there is only sparse information about PTEN protein expression in hormone-dependent female tumors. Therefore, we investigated PTEN expression in 68 breast and 43 endometrial carcinomas. METHODS: For PTEN protein detection, we used Western blot analysis followed by densitometry and compared these data with clinicopathologic parameters, the estrogen receptor (ER) and progesterone receptor (PR) status, HER2/neu and the proliferation marker Ki67. RESULTS: We were able to show significantly decreased PTEN protein expression in endometrial carcinomas compared with normal endometrial tissue samples, especially in the endometrioid histological subtype. In contrast, PTEN downregulation was found more rarely in breast cancer. Lower PTEN expression in breast cancer correlated significantly with high ER immunoreactivity (p = 0.008) and was weakly associated with PR expression (p = 0.055) and low histological grading (p = 0.081). No correlation with any of these parameters was observed in endometrial tumors. In both tumor types, no association of PTEN expression with any other analyzed parameter was found. CONCLUSIONS: These results suggest that PTEN expression plays different roles in the pathogenesis of endometrial carcinomas and breast cancer. In mammary carcinomas, loss of PTEN expression is mainly found in more differentiated tumors and is probably not a major event in carcinogenesis.

Adenocarcinoma↗
PubMed2001

Frequent p16/MTS1 inactivation in early stages of urothelial carcinoma of the bladder is not associated with tumor recurrence.

OBJECTIVE: p16, located at chromosome 9p21, is a negative regulator of G1 cell checkpoint and functions as tumor suppressor gene. Only few data are available on the frequency and clinical relevance of p16 alterations in Ta, T1 transitional cell carcinoma (TCC) of the bladder. We investigated 40 patients with Ta, T1 TCC of the bladder for p16 alterations (mutations, homozygote deletions, allelic loss) or reduced p16 immunoreaction. PATIENTS AND METHODS: DNA was prepared from microdissected tumor tissue from 40 patients with pTa, pT1 TCC of the bladder (pTa: 18 patients; pT1: 22 patients; grade 1: 7 patients; grade 2: 28 patients; grade 3: 5 patients). Mutation screening was performed using polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) and direct sequencing at exon 1 and exon 2. Detection of homozygote deletions was performed using multiplex PCR. Immunohistochemistry (IHC) was performed using an anti-human monoclonal antibody (p16, Pharmingen). Allelic loss was detected by PCR using three different microsatellite markers (D9S161, D9S171, D9S319). RESULTS: SSCP and direct sequencing revealed 3 cases of base substitution which turned out to be natural polymorphisms. Homozygote deletions were not detected in any case. p16 IHC revealed reduced p16 expression (<5% positive nuclei) in 10 patients; 30 patients had a positive reaction (> or =5% positive nuclei) and 10 patients a strong positive reaction (> or =50% positive nuclei). Thirteen of 37 informative cases revealed loss of heterozygosity (LOH) with at least one marker. After a median follow-up of 23 months, 15 patients suffered from disease recurrence. Statistical analysis using Kaplan-Meier analysis and the log-rank test did not reveal significant association of recurrence-free interval and detection of LOH (p = 0.34) or p16 IHC (p = 0.9). CONCLUSIONS: We present a comprehensive evaluation of chromosome 9p21 alterations including p16 analysis and clinical follow-up data. Although p16 mutations and homozygote deletions are rarely detectable in Ta, T1 TCC, the reduction of p16 expression and the frequent hemizygote deletions at 9p21 suggest an early involvement of chromosome 9p and p16 in superficial TCC.

Carcinoma, Transitional Cell↗
PubMed2001

The glucocorticoid receptor is specifically expressed in the stromal compartment of the human endometrium.

The human endometrium is a classical target tissue for steroid hormones. While the expression pattern and functional roles of both the estrogen receptor (ER) and the progesterone receptor (PR) are well defined, expression of the glucocorticoid receptor (GR) in this tissue has not been described so far. In the present study, we used immunohistochemistry to analyze the expression of GR in the normal human endometrium throughout the menstrual cycle. The expression of GR was compared to that of ER and PR, which were analyzed in parallel. We show that GR is expressed in the human endometrium with a pattern that markedly differs from the expression patterns of ER and PR. ER and PR are expressed in the nuclei of endometrial glands, whereas GR is completely absent from these structures. However, GR is strongly expressed in the stromal compartment of the endometrium throughout the cycle. Both stromal fibroblasts and lymphocytes are GR-positive. In addition GR expression is also observed in the endothelium of small endometrial blood vessels, which are ER- and PR-negative. Western blot analysis performed on endometrial tumor cell lines of glandular (HEC-1B) and mesodermal (SKUT-1B) origin, respectively, showed GR expression only in the latter. In summary, we demonstrate that GR is expressed in fibroblasts, lymphocytes and endothelial cells of the human endometrial stroma, while it is absent from the glandular compartment. The specific expression pattern of GR within the human endometrium points to a possible functional role of glucocorticoids in the process of decidualization which occurs primarily in the stromal compartment.

Adult↗
PubMed2001

Expression and tissue localization of soluble guanylyl cyclase in the human placenta using novel antibodies directed against the alpha(2) subunit.

The cytoplasmic or soluble forms of guanylyl cyclase (sGC) are heme-containing heterodimeric enzymes that are regulated by nitric oxide (NO) and carbon monoxide (CO). These gaseous messenger molecules are produced in the human placenta and are potential regulators of vasodilation and trophoblast invasion. The alpha(2)-subunit of sGC has only recently been shown to naturally occur in placental extracts. In the present study, two novel antibodies directed against different epitopes of the alpha(2) subunit, were generated. Western Blot analysis confirmed the presence of a 82 kDa protein, identical with alpha(2) protein overexpressed in Sf9 cells. According to RNase protection analysis the alternatively spliced alpha(2i) variant was absent from human placenta. Immunohistochemical analysis showed the presence of alpha(2) protein in syncytiotrophoblast and villous and umbilical blood vessels, which are known sites of NO production. Strong expression was observed in the extravillous (intermediate) trophoblast, where the expression of CO-generating hemeoxygenases has recently been documented. Localization of alpha(2) subunit expression suggests a role for sGC in mediating the actions of both NO and CO. The novel antibodies characterized in the present study will be powerful tools to further elucidate the role of the NO/CO/cGMP signaling pathways in pathologic states such as preeclampsia and intrauterine growth retardation.

Amino Acid Sequence↗
PubMed2000

Expression of cell cycle-regulatory proteins rb, p16/MTS1, p27/KIP1, p21/WAF1, cyclin D1 and cyclin E in breast cancer: correlations with expression of activating protein-1 family members.

The activating protein-1 (AP-1) complex is a mitogen-activated composite transcription factor that leads to activation of various target genes and enhanced proliferation of many cells after stimulation by TPA, EGF, serum, etc. The molecular mechanism of cell-cycle activation by AP-1 complexes remains unclear. Therefore, we studied protein expression of 6 cell cycle-regulatory proteins (Rb, p16, p21, p27, cyclin D1, and cyclin E) in protein extracts from 53 breast cancer samples and 4 mammary cell lines and correlated the data with expression of the 7 AP-1 family members (c-jun, junB, junD, c-fos, fosB, fra-1, and fra-2) as determined in a previous study. After Western blot analysis, we found significant associations between members of both groups: whereas c-jun was associated with Rb expression (p = 0.002), strong junD and c-fos expression correlated with high cyclin E reactivity (p = 0.017 and p = 0.013, respectively). Over-expression of fosB was found mainly in tumors with strong Rb (p = 0.013) and weak p16 (p = 0.004) expression. Fra-1 expression was significantly associated with p16 and cyclin E over-expression, whereas fra-2 results correlated with both cyclin D1 and cyclin E. These results point to direct or indirect activation of some cell cycle-regulatory proteins by AP-1 complexes. In addition, our data suggest differential regulation of cell cycle-stimulating and -inhibiting factors depending on the abundance of single AP-1 family members.

Blotting, Western↗
PubMed2000

Association of human papillomavirus infection with carcinoma of the cervix uteri and its precursor lesions: theoretical and practical implications.

Human papillomaviruses (HPVs) are the major aetiological agents of cervical carcinoma. In this review, epidemiological and molecular data are combined to present a model for HPV-induced cervical carcinogenesis. The impact of current knowledge regarding diagnostic and therapeutic approaches is shown, i.e. the use of HPV tests in cervical cancer screening, in the management of atypical smears of uncertain diagnosis and in smears indicative of mild dysplasias, as well as in follow-up examinations during and after therapy. In addition, the value of the two most frequently used HPV detection systems, polymerase-chain reaction (PCR) and hybrid capture (HC) analysis, is discussed.

Female↗
PubMed2000

Differences in HPV 16- and HPV 18 E6/E7 oncogene expression between in situ and invasive adenocarcinomas of the cervix uteri.

To evaluate the importance of high-risk human papillomavirus (HPV) types in in situ and invasive adeno- and adenosquamous carcinomas (ACISs/ACs, and ASCISs/ASCs) of the cervix uteri, we analyzed HPV infection and HPV 16- and HPV 18 E6/E7 oncogene expression in different histologic subtypes. Using the polymerase chain reaction (PCR) technique, 29 of 33 (88%) ACISs, 2 of 2 (100%) ASCISs, 46 of 54 (85%) ACs, and 8 of 10 (80%) ASCs were found to be HPV 16- and/or HPV 18-positive. In 25 of 35 (71%), 10 of 35 (29%), and 4 of 35 (11%) ACISs/ASCISs, HPV 16, HPV 18, and HPV 16 and HPV 18 were detected, respectively. Invasive ACs/ASCs were more frequently infected with HPV 18 (36 of 64, 56%) than with HPV 16 (28 of 64, 44%). Ten (16%) of these cases were positive for HPV 16 and HPV 18. In ACISs/ASCISs, HPV 16 oncogene expression predominated (62%) relative to HPV 18 (25%) expression, whereas in invasive ACs/ASCs, only 21% of the cases expressed HPV 16, but 48% of the cases expressed HPV 18 oncogenes. Thus, detection of HPV 18 in ACISs/ASCISs might be associated with an increased risk of progression. HPV oncogene expression was not dependent on histologic subtype of in situ or invasive AC. Normal glandular epithelia and glandular dysplasias (GDs, n = 4) were always negative concerning HPV oncogene expression. In HPV 16- and HPV 18-double-infected cases, HPV 18 oncogene expression was most frequently detected, and we did not find a coexpression of HPV 16- and HPV 18-specific oncogenes in purely glandular lesions or in cases with an additional CIN (cervical intraepithelial neoplasia) II or CIN III. HPV E6/E7 expression of the same HPV type in both in situ or invasive ACs and associated CIN II/III suggest that these lesions might be histogenetically related.

Adenocarcinoma↗
PubMed2000

The adhesion molecule CEACAM1 (CD66a, C-CAM, BGP) is specifically expressed by the extravillous intermediate trophoblast.

CEACAM1 (CD66a, C-CAM, BGP) is an adhesion molecule of the carcinoembryonic antigen family which has been shown to be normally expressed at the apical pole of epithelial cells, including the apical pole of endometrial surface and glandular epithelia. The purpose of the present study was to investigate its expression pattern at the maternal-fetal interface, and thus to determine whether CEACAM1 could be implicated in the human implantation process. For this purpose, we performed immunohistochemistry using the 4D1/C2 monoclonal antibody (mAb) as well as flow cytometry and Western blot on isolated trophoblast populations. On the maternal side of the maternal-fetal interface, CEACAM1 was present in epithelial cells of pregnancy endometrium as well as in small endometrial vessels, whereas it was absent from decidual cells. On the fetal side, CEACAM1 was strongly expressed by the extravillous (intermediate) trophoblast at the implantation site, as well as by extravillous trophoblast cells with invasive phenotype in primary culture, as shown by flow cytometry and Western blot. Expression was also observed in placental villous core vessels but was absent from both villous cyto- and syncytiotrophoblasts throughout the pregnancy. We conclude that, given its specific expression pattern, CEACAM1 can be a useful marker for extravillous intermediate trophoblast and might be functionally implicated in mediating trophoblast/endometrial and/or trophoblast/endothelial interactions during the trophoblastic invasion of the endometrium.

Antigens, CD↗
PubMed2000

Progesterone receptor isoforms, PR-B and PR-A, in breast cancer: correlations with clinicopathologic tumor parameters and expression of AP-1 factors.

In the present study, we used Western blot analysis to determine the expression of the progesterone receptor (PR) isoforms, PR-B and PR-A, in breast tumors (n = 53), and correlated the expression patterns of the two isoforms with the clinicopathological parameters of these tumors and with expression of the AP-1 family of transcription factors. Expression of the two PR isoforms correlated significantly with each other, indicating that the expression of the two isoforms is probably regulated in a correlated fashion. Expression of both isoforms correlated significantly with expression of the estrogen receptor (ER). Furthermore, expression of PR-B was found to correlate significantly with the absence of ErbB2/neu. For the AP-1 factors, Fra-1 expression showed an inverse correlation with PR-B expression. In contrast, expression of FosB correlated significantly with expression of both isoforms, and the association was stronger with PR-B expression. An analysis of the ratio of expression of the two isoforms showed that most of the tumors expressed PR-A levels which were equal or higher than the corresponding PR-B expression levels (together 94% of the analyzed tumors) indicating that, in mammary carcinomas, a predominance of the PR-A isoform over the PR-B isoform seems to be the case. While there was no statistically significant correlation with age, staging and histological type, expression of both isoforms correlated with a more differentiated phenotype (G1/G2 grading). However, this association was stronger for PR-B. Also, a PR-A < or = PR-B expression level was associated with G1/G2 grading, while a PR-A > PR-B expression level showed an association with a more undifferentiated phenotype (G3 grading). The expression level of the two PR isoforms might prove to be of prognostic and/or predictive value, especially since the two isoforms have been shown to be functionally different and to modulate the response of tumor cells to progestins and antiprogestins differently.

Blotting, Western↗
PubMed2000

Leukemia inhibitory factor (LIF) stimulates the human HLA-G promoter in JEG3 choriocarcinoma cells.

HLA-G is a non-classic class I MHC molecule specifically expressed by human invasive cytotrophoblast cells, which has been suggested to play a role in facilitating the immune tolerance of the conceptus. So far, very little is known about the regulation of the human HLA-G gene. The present study was, thus, designed to investigate the regulation of the human HLA-G promoter. JEG3 choriocarcinoma cells, which express HLA-G endogenously, were used as a model. A 890 bp fragment of the human HLA-G promoter was amplified by nested PCR from genomic DNA, cloned into pCR-Script and, after sequencing, subcloned into pGL3-Luc in front of the luciferase reporter gene. This vector was then used in transient transfection experiments in JEG3 cells. Parallel transfection experiments were performed using an alpha subunit (alphaSU)-Luc reporter plasmid as a control. Using this system, several potential modulating substances were tested in different concentrations and for different periods of time: phorbol ester (TPA), cAMP, IFNgamma, IL-1, and leukemia inhibitory factor (LIF), with only LIF administration resulting in induction of the HLA-G promoter. LIF treatment also resulted in induction of HLA-G mRNA. JEG3 cells are shown to possess LIF receptors. LIF is a pleiotropic cytokine produced at the maternal-fetal interface which has been shown to play an essential role in implantation in mice. LIF is produced in high amounts by the human endometrium and the trophoblast itself, and LIF receptors are present on cytotrophoblast cells. LIF could, thus, play a role in modulating HLA-G production and immune tolerance at the maternal-fetal interface.

Animals↗
PubMed2000

Telomerase activity and expression of the telomerase catalytic subunit, hTERT, in meningioma progression.

OBJECT: In recent reports, 6 to 19% of meningiomas have been classified as atypical or anaplastic/malignant. Some atypical and anaplastic meningiomas appear to arise from benign tumors by progression. Telomerase activation has recently been associated with malignant progression of human tumors. The authors have investigated a series of benign, atypical, and anaplastic/malignant meningiomas for telomerase activity and expression of the telomerase catalytic subunit human telomerase reverse transcriptase (hTERT). METHODS: A quantitative telomeric repeat amplification protocol was used to detect telomerase enzyme activity in seven (21%) of 34 benign, but in nine (75%) of 12 atypical and in seven (100%) of seven anaplastic/malignant meningiomas. Very high levels of telomerase activity were observed only in highly aggressive tumors. Messenger (m)RNA expression of the catalytic subunit hTERT was found in 11 (33%) of 33 benign, 12 (92%) of 13 atypical, and all seven anaplastic/malignant tumors. All telomerase-positive lesions were also positive for hTERT mRNA, whereas no telomerase activity was detected in six (21%) of 29 hTERT-positive tumors. This indicates that upregulation of hTERT is the rate-limiting step for telomerase activation in the majority of meningiomas. Expression of telomerase and hTERT was seen in all four tumors with gross brain invasion. All recurrent tumors or meningiomas recurring during follow up expressed hTERT. CONCLUSIONS: The results are consistent with a role for telomerase activation during the development of malignancy in meningiomas. Hence, expression of telomerase activity and hTERT might prove to be potentially useful markers for the evaluation of these tumors.

Adult↗
PubMed1999

Expression pattern of the AP-1 family in breast cancer: association of fosB expression with a well-differentiated, receptor-positive tumor phenotype.

In the present study, the expression of members of the AP-1 family of transcription factors in breast tumors (n = 53) was investigated by Western blot with antibodies specific for each of the AP-1 family members (c-jun, junB, junD and c-fos, fosB, fra1 and fra2). The tumors were characterized with regard to grading, staging, histology, steroid-receptor-expression status and c-erbB2/neu expression. For comparison, normal breast-tissue samples, human breast-cancer cell lines (T47D and MDA-MB231) and the transformed human breast epithelial cell line HBL100 were also analyzed. For c-jun, junB, c-fos and fra2, a relatively uniform expression pattern without significant differences among tumors was observed. junD-protein amounts varied strongly in the tumor specimens. fosB-expression levels also varied strongly in the tumors, weak/absent expression being found in 47%, while 45% exhibited strong/very strong levels of expression. While none of the other AP-1 family members showed significant correlations with clinico-pathological tumor parameters or receptor status, expression of fosB was found to correlate significantly with positive steroid-hormone-receptor status (in the tumors and the cell lines) and a more differentiated tumor phenotype. Expression of 2 fra-1-specific bands of 33 and 36.5 kDa showed significant negative correlation with fosB expression, as well as with estrogen-receptor status and differentiation. We conclude that strong differences in the expression pattern of AP-1 family members are present in breast tumors, and that certain members of this family, such as fosB and fra-1, might be involved in the pathogenesis of these tumors.

Breast Neoplasms↗
PubMed1999

Differential telomerase activity, expression of the telomerase catalytic sub-unit and telomerase-RNA in ovarian tumors.

Telomerase activity has been found in a variety of malignant tumors but only rarely in benign tumors or normal tissues. In this study, we investigated telomerase activation in 37 ovarian tumors, including benign, borderline and malignant neoplasms. Telomerase activity was detected using the telomeric repeat amplification protocol (TRAP) in 13/16 ovarian carcinomas, 9/10 borderline tumors and 3/11 cystadenomas/fibromas. mRNA expression of the putative human telomerase catalytic sub-unit gene (hTERT) was detected by RT-PCR in 14/15 ovarian carcinomas, 8/10 borderline tumors and 4/11 cystadenomas/fibromas. In situ hybridization was performed to evaluate telomerase-RNA (hTR) expression in the corresponding paraffin-embedded tumors. Variable expression levels of hTR were found over neoplastic tumor cells. The highest levels of hTR expression were found predominantly in ovarian carcinomas. Although the amount of telomerase activity varied, significantly high levels of telomerase activity were found predominantly in ovarian carcinomas. hTERT mRNA expression was closely associated with telomerase activity. These findings suggest that up-regulation of hTERT and hTR is important for telomerase activation during malignant-tumor progression. Telomerase activation might therefore be a valuable diagnostic parameter that could help to identify potentially progressive lesions. However, the diagnostic and therapeutic implications of telomerase activation need to be clarified in clinical trials. Int. J. Cancer (Pred. Oncol.) 84:426-431, 1999.

Cystadenoma↗