Biomedical subjects

M Takakura

Publications and source records attributed to M Takakura.

At least 37 records · Page 2Linked to original sources

PubMed2000

Adenoviral expression of p53 represses telomerase activity through down-regulation of human telomerase reverse transcriptase transcription.

Telomerase activation is a critical step in cellular immortality and oncogenesis. The activity of telomerase is known to be correlated with cell proliferation, but its regulation by cell cycle regulators is not well understood. In the present study, we examined the effects of p53 on telomerase activity. Wild-type p53 was introduced into SiHa cells via a recombinant adenoviral vector, Ad5CMV-p53, and change in telomerase activity was examined by quantitative telomerase assay. Telomerase activity in the Ad5CMV-p53-infected cells was significantly repressed 36 h after infection following down-regulation of human telomerase catalytic subunit [human telomerase reverse transcriptase (hTERT)] mRNA expression, whereas no change in telomerase activity was observed in the cells infected with control vector AdSCMV-beta-gal. Interestingly, repression of telomerase activity was an early event that preceded cell growth inhibition or apoptosis induced by p53 overexpression, suggesting that p53 directly regulates telomerase activity. Transient expression assays using hTERT-promoter reporter constructs revealed that overexpression of p53 significantly repressed promoter activity of hTERT. 5'-Truncation of the promoter sequences revealed that the proximal core promoter region containing multiple binding sites for transcription factor Spl was responsible for p53-mediated transcriptional repression. Mutations in these binding sites for Spl led to failure of p53 to repress transcription. These findings suggest that p53 repressed telomerase activity through down-regulation of hTERT transcription and that interaction of p53 with Sp1 or other transcription factors may be involved in this regulation.

Adenoviridae↗

PubMed2000

Demethylating reagent 5-azacytidine inhibits telomerase activity in human prostate cancer cells through transcriptional repression of hTERT.

Telomerase activation is thought to be a critical step in cellular immortality and oncogenesis. Several reagents including differentiation-inducing and antineoplastic agents are known to inhibit telomerase activity, although the molecular mechanisms through which they inhibit telomerase activity remain unclear. Demethylating reagents have recently been used as potential antineoplastic drugs for some types of cancers including those of the prostate. In the present study, we examined the effect of the demethylating reagent 5-azacytidine (5-aza-CR) on telomerase activity using cells of two prostate cancer cell lines, DU-145 and TSU-PR1. 5-aza-CR treatment significantly reduced telomerase activity in TSU-PR1 cells, but not in DU-145 cells, although growth inhibition was observed to a similar extent in both cell lines. Reverse transcription-PCR analyses revealed that inhibition of telomerase activity was accompanied by down-regulation of telomerase catalytic subunit (hTERT) mRNA expression. Transient expression assays showed that 5-aza-CR repressed the transcriptional activity of the hTERT promoter and that the E-box within the core promoter was responsible for this down-regulation. Western blot analyses revealed that 5-aza-CR reactivated p16 expression and repressed c-Myc expression in TSU-PR1 cells but not in DU-145 cells. Overexpression of p16 in TSU-PR1 cells led to significant repression of c-Myc transcription. These findings suggest that 5-aza-CR inhibits telomerase activity via transcriptional repression of hTERT, in which p16 and c-Myc may play a key role.

Azacitidine↗

PubMed1999

Estrogen activates telomerase.

Telomerase activity is present in most malignant tumors and provides a mechanism for the unlimited potential for division of neoplastic cells. Although telomerase is known to be a regulated enzyme, the factors and mechanisms involved in telomerase regulation are not well understood. In the present study, we examined the effects of estrogen on telomerase activity. Telomerase activity in estrogen receptor (ER)-positive MCF-7 cells was up-regulated by the treatment with 17beta-estradiol. This activation accompanied up-regulation of the telomerase catalytic subunit, hTERT mRNA. Gel shift assays revealed that the imperfect palindromic estrogen-responsive element in the hTERT promoter specifically binds to ER. Transient expression assays using luciferase reporter plasmids containing various fragments of hTERT promoter showed that this imperfect palindromic estrogen-responsive element is responsible for transcriptional activation by ligand-activated ER. We also found that estrogen activates c-Myc expression in MCF-7 cells and that E-boxes in the hTERT promoter that bind c-Myc/Max play additional roles in estrogen-induced transactivation of hTERT. Estrogen thus activates telomerase via direct and indirect effects on the hTERT promoter. These findings may help elucidate the mechanisms of hormonal control of telomerase activity and aid understanding of the roles of sex steroids in cellular senescence and aging as well as estrogen-induced carcinogenesis.

Base Sequence↗

PubMed1999

Expression of human telomerase subunits in ovarian malignant, borderline and benign tumors.

Telomerase activity is involved in the maintenance of telomere length and is thought to be required for cellular immortality and oncogenesis. Three major subunits composing telomerase, human telomerase RNA (hTR), telomerase-associated protein (TPI) and human telomerase catalytic subunit (hTERT), have been identified. However, their functions and the regulatory mechanisms by which telomerase is activated have not been fully determined. In the present study, a total of 35 epithelial ovarian cancers, 5 ovarian low potential malignancies (LPM), 11 ovarian benign cysts and 12 normal ovaries, as well as various cell lines derived from ovarian cancers, were examined for the expression of hTR, TPI mRNA and hTERT mRNA. Correlations of expression with telomerase activity were evaluated. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that hTR and TPI mRNA were expressed in more than 80% of ovarian cancers, LPM, ovarian cysts and even in normal ovaries. However, hTERT mRNA was observed only in ovarian cancers, most of which exhibited telomerase activity. Normal ovarian tissues, ovarian cysts and LPM, most of which had no telomerase activity, did not express hTERT. Five telomerase-positive ovarian cancer cell lines expressed each of the telomerase subunits, whereas 2 telomerase-negative normal primary fibroblast cell lines expressed TPI mRNA and hTR, but not hTERT mRNA. There was a significant correlation of telomerase activity with hTERT mRNA expression but not with TPI or hTR expression. Expression of hTERT is thus specific to cancer lesions and appears to be a rate-limiting determinant of the enzymatic activity of human telomerase. Up-regulation of hTERT may play a critically important role in the development of ovarian cancers.

Adenocarcinoma, Clear Cell↗

PubMed1999

Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells.

Telomerase activation is thought to be a critical step in cellular immortalization and carcinogenesis. Of the three major subunits comprising human telomerase, human telomerase catalytic subunit (hTERT) has been shown to be a rate-limiting determinant of the enzymatic activity of human telomerase. However, little is known concerning how expression of hTERT is regulated in human cells. To identify the regulatory elements controlling hTERT gene expression, approximately 3.5 kb of the 5'-flanking sequence of hTERT was cloned and characterized. The promoter of hTERT was GC rich and lacked both TATA and CAAT boxes. The CapSite Hunting method identified transcription start site 19 bp upstream of the first nucleotide of the published cDNA sequence. Transient expression assays revealed that transcription of hTERT was significantly activated in cancer cell lines but repressed in normal primary cells. Using the fibroblast lineage at various stages of transformation, we found that transcription occurred in strains that had overcome replicative senescence and expressed telomerase activity. Deletion analysis of hTERT promoter identified the 181-bp core promoter region upstream of the transcription start site. Gel shift analysis revealed two major factors binding to core promoter, an E box (CACGTG) binding factor and Sp1. Overexpression of c-Myc resulted in a significant increase in transcriptional activity of the core promoter. These findings suggest that hTERT expression is strictly regulated at the transcription machinery, and that the proximal core promoter containing an E box and Sp1 sites is required for transactivation of hTERT.

Base Sequence↗

PubMed1999

Human telomerase reverse transcriptase as a critical determinant of telomerase activity in normal and malignant endometrial tissues.

Telomerase activation is thought to be essential for cellular immortality and oncogenesis. It is observed in most malignant tumors but not in most normal somatic tissues. Normal human endometrium is, however, known to express significant telomerase activity in a menstrual phase-dependent manner. The 3 major subunits composing telomerase have been identified. Using normal and malignant endometrial tissues, we studied how these components are involved in telomerase activation. A total of 23 endometrial cancers and 32 normal human endometria in various menstrual phases as well as cell lines derived from endometrial cancer were examined for the expression of each telomerase subunit using RT-PCR analysis. Telomerase activity in each sample was determined by the TRAP assay, and the correlation between subunit expression and telomerase activity was examined. RT-PCR analysis revealed that telomerase RNA (hTR) and telomerase-associated protein (TP1) mRNA were constitutively expressed in both normal and malignant endometrial tissues. Expression of human telomerase reverse transcriptase (hTERT) mRNA was observed in most endometrial cancers, while that in normal endometrium depended on the phases of menstrual cycles. Proliferative phase normal endometria expressed hTERT mRNA, while secretory phase endometria did not. There was a strong association between telomerase activity and hTERT expression but not TP1 or hTR expression in both normal and tumor tissues. Five telomerase-positive endometrial cancer cell lines expressed each of the telomerase subunits including hTERT, while 2 telomerase-negative normal primary fibroblast cells expressed TP1 mRNA and hTR, but not hTERT mRNA. Our findings suggest that hTERT is a rate-limiting determinant of enzymatic activity of human telomerase. Since some normal tissues with high regenerative potential can express hTERT, special attention should be paid to the clinical use of hTERT inhibitors as anti-cancer drugs.

Carrier Proteins↗

PubMed1998

hTERT is a critical determinant of telomerase activity in renal-cell carcinoma.

Telomerase is a ribonucleoprotein enzyme which stabilizes chromosomal structure, thereby inducing cellular immortality. Three major subunits composing telomerase complex have been cloned, designated hTR (human telomerase RNA), TPI (telomerase-associated protein I), and hTERT (human telomerase reverse transcriptase). In the present study, a total of 36 renal-cell carcinomas (RCC) and adjacent normal tissues, as well as cell lines derived from RCC or normal kidney, were examined for the expression of each telomerase subunit and telomerase activity. RT-PCR analyses revealed that hTR and TP I mRNA were constitutively expressed both in tumor and in normal tissues. In contrast, hTERT mRNA was expressed in most tumors, but not in normal tissues. Telomeric-repeat-amplification-protocol (TRAP) assay revealed that more than 80% of RCC tumor tissue exhibited telomerase activity, while none of the adjacent normal tissue did. There was a significant association of telomerase activity with expression of hTERT mRNA, but not with TPI mRNA or hTR expression. Two cell lines, derived from RCC and cervical cancer, expressed telomerase activity and hTERT mRNA, while normal renal cortical epithelial cells expressed neither of them. These findings suggest that hTERT plays a critical role in determining the enzymatic activity of human telomerase, and that up-regulation of hTERT probably plays a role in the progression of human cancers.

Adult↗

PubMed1998

Expression of human telomerase subunits and correlation with telomerase activity in cervical cancer.

Activation of telomerase and stabilization of telomeres are thought to be required for both cellular immortality and oncogenesis. Three major components of human telomerase, human telomerase RNA (hTR), telomerase-associated protein (TP1/TLP1), and human telomerase catalytic subunit (hTRT/hEST2), have been identified recently. However, it remains unclear what roles these subunits play in the regulation of telomerase activity. In the present study, a total of 25 cervical cancers and 14 normal cervices as well as various cell lines derived from cervical cancer were examined for the expression of hTR, TP1 mRNA, and hTRT mRNA, and the correlations between expression of these and telomerase activity were evaluated in 23 cancers and 14 normal cervices. Reverse transcription-PCR analysis revealed that hTR and TP1 mRNA were commonly expressed in cancers and noncancerous tissues. However, hTRT mRNA was observed only in cervical cancers and cell lines, and more than 80% of cervical cancers expressed it, whereas neither normal cervical tissues nor normal primary fibroblast cells did. There was a strong correlation of telomerase activity with hTRT mRNA expression but not with TP1 or hTR expression. Cervical exfoliated cells were subjected to reverse transcription-PCR analysis for detection of hTRT mRNA, and approximately 70% of cervical cancers were positive for such expression. These findings provide strong evidence that expression of hTRT is a rate-limiting determinant of the enzymatic activity of human telomerase and that up-regulation of hTRT expression may play a critical role in human carcinogenesis. Our findings also indicate that detection of hTRT mRNA is useful for cytological screening for cervical cancer.

Carrier Proteins↗

PubMed1998

Telomerase activity in cervical cancer is quantitatively distinct from that in its precursor lesions.

Studies using the telomeric repeat amplification protocol (TRAP) assay have demonstrated telomerase activity not only in cancers but also in non-cancerous lesions. However, quantitative differences in activity between both lesions have not been examined. In the present study, using a stretch PCR assay, telomerase activity was analyzed quantitatively in cervical cancer, its precursor squamous intra-epithelial lesions (SILs) and normal cervix. In stretch PCR assay, telomerase activity was expressed in relative units vs. control activity from C33A cells (100 units). Mean telomerase activities in cervical cancer, SIL and normal cervix were 72+/-35 units, 18+/-17 units and 7+/-4 units, respectively, suggesting that telomerase activity in cancer lesions was quantitatively distinct from that in pre-malignant lesions, which may mean a much more pronounced activation of telomerase in cancers than in SIL. Our findings also suggest that stretch PCR assay can distinguish telomerase activity in cancer from that in non-cancerous lesions and may be useful for the differential diagnosis of cancer lesions.

Adenocarcinoma↗

PubMed1998

Ovarian endometrioid adenocarcinoma with ectopic production of alpha-fetoprotein.

alpha-Fetoprotein (AFP) is well known as a tumor marker of ovarian endodermal sinus tumor or embryonal carcinoma in gynecological malignancies. However, AFP production is extremely rare in ovarian epithelial cancers. Here we report a case of a 53-year-old woman with an AFP-producing ovarian endometrioid adenocarcinoma. The serum AFP level was elevated up to 2759 ng/ml preoperatively, with a subsequent decrease to the normal range after treatment. Histological examination of the tumor revealed a well-differentiated endometrioid adenocarcinoma with small foci of clear cell components. None of endodermal sinus tumor, hepatoid carcinoma, or embryonal carcinoma components were observed. Immunohistochemical analysis revealed that AFP was expressed in the cytoplasm of the endometrioid glandular lesions, but not in the clear cell components. This is probably the first case of a pure type of ovarian endometrioid adenocarcinoma with significant levels of AFP expression.

Adenocarcinoma↗

PubMed1998

Expression of telomerase activity in human endometrium is localized to epithelial glandular cells and regulated in a menstrual phase-dependent manner correlated with cell proliferation.

Telomerase activity is observed in most malignant tumors and germ cells, whereas normal somatic cells usually do not express it. Human endometrium is composed of glandular and stromal components and exhibits dramatic changes in proliferative activity during the menstrual cycle, which is exquisitely regulated by estrogen function. We previously reported that normal human endometrium expresses telomerase activity. However, it remains unclear which of the above components are the major sources of telomerase activity and how levels of telomerase activity are regulated over the menstrual cycle. Quantitative analysis of telomerase activity revealed that it changes dramatically over the course of the menstrual cycle and is strictly regulated in a menstrual-phase-dependent manner. Maximal activity equivalent to that in endometrial cancer was present in late proliferative phase, and minimal activity in late secretory phase. Postmenopausal endometrium and endometrium treated with anti-estrogen drugs exhibited decreased telomerase activity. Testing isolated epithelial glandular cells and stromal cells, we found that telomerase activity was localized to epithelial glandular cells. In situ RNA hybridization analysis also revealed epithelial-specific expression of human telomerase RNA. In vitro analysis of cultured epithelial cells demonstrated that telomerase activity is correlated with epithelial proliferation but not affected by estrogen treatment. These findings suggest that expression of telomerase activity is specific to epithelial cells and linked to cell proliferative status. The involvement of estrogen in telomerase regulation remains to be elucidated.

Cell Division↗

PubMed1998

[Analysis of zinc concentrations in leukocytes and its application to patients with non-insulin-dependent diabetes mellitus].

Zinc concentrations in leukocytes of healthy subjects and patients with NIDDM were determined by inductively coupled plasma mass spectrometry. Lymphocytes and granulocytes were isolated from whole blood by discontinuous gradients of mono-poly resolving medium and flow cytometry. Flow cytometry was used for isolating lymphocytes and granulocytes from mononuclear and polymorphonuclear leukocytes. The results in healthy subjects and patients with NIDDM were as follows: lymphocytes of healthy male and female subjects were 49.8 +/- 1.0 (mean +/- SE, microgram per 10(10) cells) and 50.0 +/- 1.4, respectively; granulocytes were 46.4 +/- 1.0 in male, 49.3 +/- 1.4 in female. Lymphocytes of male and female patients with NIDDM were 43.3 +/- 0.9 and 43.1 +/- 1.7, respectively; granulocytes, 41.2 +/- 1.4 in male, 43.8 +/- 1.0 in female. There was a significant difference in the zinc concentrations of lymphocytes and granulocytes between healthy subjects and patients with NIDDM. However, there was no significant difference in the zinc concentrations of lymphocytes and granulocytes between male and female. In healthy subjects, zinc concentrations of lymphocytes and granulocytes significantly lowered with aging.

Adult↗

PubMed1998

Morphologic analysis of dentofacial structure in patients with acromegaly.

The purpose of this study was to investigate the morphologic changes of the oral and maxillofacial skeletal structure in patients with acromegaly and the correlation between growth hormone, age at onset, and duration. Fifty-four acromegalic patients (28 men and 26 women) were compared with 45 normal adults (23 men and 22 women) using casts and cephalometric analysis. The incisor relationship was classified into four types: edge-to-edge bite, crossbite, maxillary incisor protrusion, and normal bite. Many cases of edge-to-edge bite and crossbite were observed in acromegalic patients. The most characteristic craniofacial skeletal differences in patients with acromegaly were protruded glabella and increased anterior face height. Enlargement of the ascending ramus and prominence of the mandible, chin, and mouth were the most noticeable profile characteristics of acromegalic patients. Male patients tended to demonstrate downward mandibular advancement and crossbite, while females showed extension of the ascending ramus, downward displacement of mandible, bimaxillary alveolar protrusion, and edge-to-edge bite.

Acromegaly↗

PubMed1998

Quantitative differences in telomerase activity among malignant, premalignant, and benign ovarian lesions.

Telomerase activation has been demonstrated in both cancers and some noncancerous lesions. However, few studies have determined levels of telomerase activity in these lesions. In the present study, using a recently developed stretch PCR assay, telomerase activity was quantitatively determined in a variety of ovarian lesions including 36 ovarian cancers, 5 ovarian low potential malignancy (LPM) lesions, 10 ovarian cysts, and 12 normal ovaries. Telomerase activity was normalized to control activity (100 units) in C33A cell line and given in relative units. Telomerase activity in ovarian cancer (51 +/- 7 units, mean +/- SE) was significantly higher than that in LPM lesions, ovarian cysts, and normal ovaries (7 +/- 3, 10 +/- 2, and 10 +/- 2 units, respectively; P < 0.001). Interestingly, all LPMs, ovarian cysts, and normal ovaries exhibited low telomerase activity less than 30 units, and no significant difference in level of telomerase activity was found among them. We also found a significant correlation between the level of telomerase activity and the clinical stage of ovarian cancer. Our quantitative telomerase assay thus clearly distinguished telomerase activity in ovarian cancers from that in LPM lesions and ovarian cysts. Significant levels of telomerase activation frequently occurred in cancer but rarely occurred in premalignant and benign lesions, suggesting that telomerase activation is a critical step in cancer development.

Female↗

PubMed1998

Expression of human telomerase subunits and correlation with telomerase activity in urothelial cancer.

The activation of telomerase and stabilization of telomeres are thought to be required for cellular immortality and oncogenesis. Three major components of human telomerase--human telomerase RNA (hTERC), telomerase-associated protein (TEP1), and human telomerase catalytic subunit (hTERT)-have recently been identified. However, the roles played by these subunits in the regulation of telomerase activity are still unclear. In the present study, a total of 37 urothelial cancers, including one metastatic lesion, and adjacent normal tissues as well as cell lines derived from bladder cancers were examined for the expression of each telomerase subunit. Reverse transcription-PCR analysis revealed that more than 90% of urothelial cancers expressed hTERT mRNA, whereas less than 20% of normal adjacent tissues did. In contrast, hTERC and TEP1 mRNA were commonly expressed in both cancers and normal tissues. All of the three cell lines derived from bladder cancer expressed each of the telomerase subunits, whereas the two normal primary fibroblast cell lines expressed hTERC and TEP1 mRNA but not hTERT mRNA. Telomerase activity was examined using telomeric repeat amplification protocol assay. All of the cancers examined exhibited telomerase activity, whereas only 2 of 12 normal tissues exhibited weak activity. There was a significant association of telomerase activity with hTERT mRNA expression but not with hTERC or TEP1 mRNA expression. These findings provide strong evidence that the expression of hTERT is a rate-limiting determinant of the enzymatic activity of human telomerase and that the up-regulation of hTERT expression may play a critical role in human carcinogenesis.

Aged↗

PubMed1998

Detection of human telomerase reverse transcriptase messenger RNA in voided urine samples as a useful diagnostic tool for bladder cancer.

Activation of telomerase and stabilization of telomeres are thought to be required for cellular immortality and oncogenesis. Telomerase activity is detected in >90% of various cancers, including urothelial cancers. Of the three subunits comprising telomerase complex, human telomerase reverse transcriptase (hTERT) is a rate-limiting determinant of the enzymatic activity of telomerase. In the present study, spontaneously voided urine specimens from 33 patients with bladder cancer and 26 without bladder lesions were examined for the expression of hTERT mRNA, and the usefulness of detecting hTERT mRNA in urine samples for screening of bladder cancer was evaluated. RT-PCR analysis revealed that approximately 80% of urinary sediments from patients with bladder cancer expressed hTERT mRNA, regardless of clinical stage or pathological grade, whereas only 4% of sediments from patients without urothelial lesions did. Interestingly, hTERT mRNA expression was observed, even in some urine samples from bladder cancer patients with negative urinary cytology. These findings suggest that the expression of hTERT in urine sample may be a useful diagnostic marker for bladder cancer.

Aged↗

PubMed1997

Expression of telomerase activity in human chorion.

Telomerase activation is required for cellular immortalization and is found in most malignant tumors. Normal somatic cells are generally telomerase-negative, except for stem cells in renewing tissues. During pregnancy, human trophoblast continues to proliferate and acts as proliferating stem cells for the development of chorion and the formation of placenta. In the present study, a total of 105 chorions from placentas at various weeks of gestation were examined for telomerase activity using the telomeric repeat amplification protocol (TRAP) assay. Twenty-five of 33 (76%) normal early chorions at 5 to 9 weeks gestation were telomerase-positive. Chorions from early spontaneous abortions also exhibited telomerase activity but at a low level. In contrast, only 2 (4%) late chorions at 34 to 41 weeks gestation expressed telomerase activity. Significant telomerase activity was observed in trophoblast cell fractions of chorion, demonstrating trophoblast to be the source of the activity. Expression of human telomerase catalytic subunit (hTRT) was observed in early chorions, but not in late placenta, and there was a close correlation between telomerase activity and hTRT expression. In contrast, expression of human telomerase RNA component (hTR) was observed in both early and late chorions and was not liked to telomerase activity. These findings suggest that telomerase activity in chorion is critically regulated over the course of gestation, associated with hTRT expression. The findings of the present study also appear to support the emerging concept that normal somatic cells with stem cell-like characteristics can express telomerase activity.

Choriocarcinoma↗

PubMed1997

Application of telomerase assay for the screening of cervical lesions.

Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends. The expression of telomerase is thought to be required for cellular immortality and oncogenesis. Telomerase activity has been detected not only in most cancers but also in some types of premalignant lesions, such as squamous intraepithelial lesions (SILs). In the present study, we used the telomerase assay to detect uterine cervical lesions in cervical scraping samples. A total of 82 cervical scraping samples were obtained from women with or without cervical lesions and examined by nonradioisotope telomeric repeat amplification protocol assay. Fifteen of 17 (88%) cervical cancer specimens exhibited telomerase activity, whereas 5 of 8 (63%) and 14 of 24 (58%) specimens from low-grade and high-grade SILs, respectively, also exhibited telomerase activity. In contrast, 3 of 33 (9%) specimens from normal cervices exhibited telomerase activity. Dilution telomeric repeat amplification protocol assay was performed to estimate telomerase activity; it revealed that high levels of activity were often expressed in cervical cancer. Cytological examination was also performed by Pap smear test, and 4 of 8 (50%) low-grade SILs, 21 of 24 (88%) high-grade SILs, and 16 of 17 (94%) cervical cancers were found to have cytological abnormalities. There were discordances in some cases between findings of smear abnormality and telomerase positivity. In particular, we found five cases of SILs without smear abnormality but with telomerase activity, suggesting that some lesions with false negative cytology can be detected by telomerase assay. These findings suggest that telomerase assay using cervical scrapings might be a useful screening method for cervical lesions especially when combined with a Pap smear test.

Biomarkers, Tumor↗