Biomedical subjects

Y Omoto

Publications and source records attributed to Y Omoto.

At least 19 recordsLinked to original sources

PubMed2004

Transcription factor EGR3 is involved in the estrogen-signaling pathway in breast cancer cells.

Estrogen has been closely associated with the genesis and malignant progression of breast cancer. However, the molecular mechanism underlying the effects of estrogen is far from being completely clarified. We previously developed a custom-made cDNA microarray consisting of approximately 200 estrogen-responsive genes in breast cancer cells. Using this system, we found one estrogen-induced gene in various cancer cell lines, including breast cancer MCF-7 cells, which encode a zinc-finger transcription factor, EGR3 (early growth response 3). Northern blot analysis of estradiol-treated MCF-7 cells showed rapid and robust induction of Egr3, and addition of cycloheximide or ICI 182,780 suggested that Egr3 is the bona fide target for the estrogen receptor alpha (ERalpha). Using stable transformants derived from MCF-7 cells which were transfected with expression-controllable Egr3-expression vector, we demonstrated that Nab2 is one of the target genes for EGR3. Microarray analysis of the transformants revealed other candidate EGR3-induced genes. These strategies could be useful for analyzing downstream genes of ERalpha, and may contribute to elucidating the extensive signaling network of estrogen stimuli. Furthermore, a reporter assay using the upstream region of fasL probably involving escape from the immune system revealed that fasL is another target gene for EGR3. The roles of EGR3 in the physiology of breast cancer are discussed.

Breast Neoplasms↗

PubMed2003

Clinical significance of AIB1 expression in human breast cancer.

AIB1 (amplified in breast cancer 1) is a member of the steroid receptor coactivator family and is a key factor in enhancing estrogen-dependent transcription. To evaluate the clinical significance of AIB1 in breast cancer, we performed Southern blot analysis of the AIB1 gene on 124 human breast cancer tissues. We also performed reverse transcription-polymerase chain reaction and semi-quantitative analysis of AIB1 mRNA expression on 58 of the tissues, and immunohistochemical detection of AIB1 protein on 115 of the tissues. On Southern blot analysis, the AIB1 gene was amplified in only two of the 124 breast cancer cases. On semi-quantitative analysis, the relative expression level of AIB1 normalized to that of GAPDH varied from 0.247 to 7.721 (median = 0.94), and was not correlated with any clinico-pathological factors. Although most of the breast cancer cells revealed cytoplasmic staining of AIB1, only 16% (18 in 115) showed nuclear staining of AIB1 protein. AIB1 nuclear expression was correlated with positivity for estrogen receptor alpha (P = 0.022). Those patients with tumor samples that showed nuclear staining of AIB1 tended to be successfully treated by endocrine therapy in comparison with those who did not show nuclear staining of AIB1. In conclusion, AIB1 nuclear expression was correlated with the estrogen receptor alpha status, and patients with AIB1 nuclear expression tended to be successfully treated by hormonal therapy.

Adult↗

PubMed2003

The expression and function of estrogen receptor alpha and beta in human breast cancer and its clinical application.

The overexpression of estrogen receptor alpha (ERalpha) is frequently observed in the early stage of breast cancer. We previously reported that the specific promoter of the ERalpha gene is responsible for this enhanced transcription of the gene, and identified the cis-acting elements which play an important role in its transcription. Furthermore, methylation of the ERalpha gene promoters also contribute to the regulation of gene transcription. Elucidation of these mechanisms of ERalpha gene expression may provide useful information for the early detection and chemoprevention of breast cancer. On the other hand, the expression of ERbeta has been reported in breast cancer. We have also assessed the significance and function of ERbeta and its variant types in breast cancer, and suggest that ERbeta and ERbetacx specifically suppress the function of ERalpha through different mechanisms. ERbeta isoforms may be important functional modulators of the estrogen-signaling pathway in breast cancer cells, and might affect the clinical outcome of patients. Moreover, to address the role of these ERs on the estrogen-dependent growth of breast cancer cells and to develop a diagnostic tool, we have analyzed the gene expression profiles of estrogen-responsive genes using cDNA microarray. Based on these results, the expression of several candidate genes in breast cancer tissues were analyzed by real-time RT-PCR and by immunohistochemical techniques, in order to discover new predictive factors for the endocrine therapy of patients with breast cancer. These studies could provide new clues for the elucidation of the estrogen-dependent mechanisms of cancer and the clinical benefits for patients.

Breast Neoplasms↗

PubMed2002

Evaluation of oestrogen receptor beta wild-type and variant protein expression, and relationship with clinicopathological factors in breast cancers.

We addressed the clinicopathological significance of the oestrogen receptor (ER) beta protein, including an ERbeta variant, ERbetacx, in normal human breast and breast cancer. The reverse transcriptase-polymerase chain reaction (RT-PCR) showed that wild-type ERbeta (ERbetaw) mRNA expression was higher in normal than cancer tissues, and that ERbetacx mRNA was higher in cancer than in normal tissues. Immunohistochemistry of 22 normal breast tissues and 57 breast cancers was performed with three different ERbeta antibodies and one ERbetacx antibody. All normal breast samples showed staining with the three ERbeta antibodies, suggesting that ERbetaw might have a physiological role in oestrogen signalling in the normal breast. In breast cancer, expression of the ERbetaw protein correlated well with the expression of the ERalpha and progesterone receptor (PgR), as well as histological grade (HG), and tended to indicate a better prognosis than when ERbetaw was absent. Thirty-one (54%) breast cancer samples contained ERbetacx, whereas the corresponding tissue for normal breast samples stained positive in only two (9%).

Adult↗

PubMed2002

Development of cDNA microarray for expression profiling of estrogen-responsive genes.

Estrogen plays an important role in many physiological events including carcinogenesis and the development of human breast cancer. However, the molecular mechanisms of estrogen signaling in cancers have not been clarified hitherto and accurate therapeutic prediction of breast cancer is earnestly desired. We first carried out estrogen-responsive expression profiling of approximately 9000 genes in estrogen receptor-positive human MCF-7 breast cancer cells. Based on the results, estrogen-responsive genes were selected for production of a custom-made cDNA microarray. Using a microarray consisting of the narrowed-down gene subset, we first analyzed the time course of the estrogen-responsive gene expression profiles in MCF-7 cells, resulting in subdivision of the genes up-regulated by estrogen into early-responsive and late-responsive genes. The expression patterns of several genes were confirmed by Northern blot analysis. We also analyzed the effects of the estrogen antagonists ICI 182780 and 4-hydroxytamoxifen (OHT) on the estrogen-responsive gene expression profiles in MCF-7 cells. While the regulation of most of the genes by estrogen was completely abolished by ICI 182780, some genes were partially regulated by estrogen even in the presence of OHT. Furthermore, the estrogen-responsive gene expression profiles of twelve cancer cell lines derived from the breast, ovary, stomach and other tissues were obtained and analyzed by hierarchical clustering including the profiles in MCF-7 cells. Several genes also showed up-regulation or down-regulation by estrogen in cell lines other than MCF-7 cells. The significance of the estrogen-responsive genes identified in these analyses concerning the nature of cancer is discussed.

Blotting, Northern↗

PubMed2001

Expression, function, and clinical implications of the estrogen receptor beta in human lung cancers.

The higher frequency of human lung adenocarcinoma in females than in males, strongly suggests the involvement of gender dependent factors in the etiology of this disease. This is the first investigation of estrogen receptor (ER) beta in human lung. Immunohistochemical staining revealed ERbeta expression in normal lung and in atypical adenomatous hyperplasia (AAH), considered as a precancerous lesion for adenocarcinomas. Adenocarcinomas showed significantly higher expression of ERbeta than squamous cell carcinomas. On the contrary, ERalpha expression was not detected in all cases. The functional integrity of ERbeta such as the binding ability to estrogen responsive element (ERE) and transcriptional activity was confirmed using a human lung cancer cell line, RERF-LC-OK. Colony formation of this cell was significantly reduced in the presence of pure antiestrogen. We conclude that ERbeta, but not ERalpha, is present in lung tissues with an important physiological function in normal lung. Furthermore, ERbeta may play a role in growth and development of adenocarcinomas.

Adenocarcinoma↗

PubMed2001

Clinical value of the wild-type estrogen receptor beta expression in breast cancer.

To estimate the clinical value of estrogen receptor (ER) beta expression in breast cancer we used an immunohistochemical method to detect the wild-type ERbeta in 88 primary breast cancers. We used a highly specific polyclonal antibody to the carboxyl terminus of wild-type ERbeta. This antibody reacted with neither other variant forms of ERbeta nor any part of ERalpha. Slides were evaluated on a scale representing the estimated proportion and intensity of positive-staining tumor cells. Positive staining could be seen in 52 (59.1%) of 88 breast cancers; 36 (40.9%) were negative. Although there was no correlation between ERbeta staining and age, node status, tumor size, histological grade, or progesterone receptor (PgR)-enzyme immunoassay (EIA) status, we did observe a significant correlation with ERalpha-EIA (Fisher's exact probability test: P=0.0169). Moreover, ERbeta positive cases showed a better prognosis than negative cases in disease-free survival rate (Logrank test: P=0.0662, Breslow-Gehan-Wilcoxson test: P=0.0318). Our data demonstrated the possibility that wild-type ERbeta protein expression could be used as a good prognostic indicator for breast cancer.

Adenocarcinoma, Mucinous↗

PubMed2001

Increase in expression of the homeobox gene, GBX1, in retinol-induced epidermal mucous metaplasia.

Using a degenerate RT-PCR-based screening method, we isolated the homeobox gene, Gbx1, from the shank skin of 13-day-old chick embryos. By in situ hybridization analysis we showed that the Gbx1 was expressed in the epidermis of the skin and the mucous epithelium of the intestine, and that among many homeobox genes isolated, expression of the Gbx1 strongly increased in the epidermis when the skin was cultured with 20 microM retinol, which induces epidermal mucous metaplasia. The Gbx1 expression in the epidermis was increased by interaction with the retinol-pretreated dermal fibroblasts, resulting in mucous metaplasia. These results suggest that the Gbx1 regulates the differentiation and transdifferentiation of the epithelium and controls the morphology of the epithelium. We isolated the chick Gbx1 cDNA clones. The amino acid sequences in homeodomain and its downstream encoded by human and chick Gbx1 cDNA were almost the same, but those upstream of the homeodomain were rather different.

Amino Acid Sequence↗

PubMed2001

Immunohistochemical analysis on biological markers in ductal carcinoma in situ of the breast.

BACKGROUND: The increasing use of mammographic screening has led to an increased detection of ductal carcinoma in situ (DCIS) of the breast. The detailed biological characteristics of DCIS and a new classification of DCIS based on these characteristics are needed. METHODS: Immunohistochemical studies were performed to assess the expression of c-erbB-2 (ErbB-2), estrogen receptor (ER), p53 and proliferative activity (Ki-67) in 65 patients with pure DCIS and 60 with invasive ductal carcinoma (IDC). We classified pure DCIS tumors using three classifications, the architectural, Nottingham, and Van Nuys classifications. RESULTS: ErbB-2, ER and p53 staining was positive in 34%, 66% and 21% of patients with DCIS, respectively, and 58%, 42% and 33% in patients with IDC, respectively. Ki-67 stained positively in 1.5% of patients with DCIS and 11.2% of patients with IDC. The comedo type showed a high rate of positive ErbB-2 and p53 staining. The cribriform and papillary types showed a high rate of positive ER staining. Under the Van Nuys classification, ErbB-2, p53 and Ki-67 expression were highest in the group with high nuclear grade and lowest in the group with non-high nuclear grade without necrosis. CONCLUSION: Although the biological markers of IDC tended to suggest aggressive behavior more so than those of DCIS, these differences were based on the histological sub-type, comedo or non-comedo. The Van Nuys classification best defined the subgroups of DCIS with a distinct expression pattern of biological markers, and the best candidates for breast-conserving surgery.

Adult↗

PubMed2001

Localization of gelatinolytic activity can be detected in breast cancer tissues by film in situ zymography.

BACKGROUND: Extracellular matrix-degrading proteinases secreted by malignant tumor cells have been thought to play an essential role in the processes of invasion and metastasis. However, existence and localization of gelatinase activity in breast cancer tissues have not been clarified. METHODS: We developed a novel film for highly reproducible detection and the localization of gelatinolytic activity. This film has a gelatin layer with a constant thickness 7 microm, and adequate crosslinking to control the speed of degradation by proteases. Cryosections of several breast cancer tissues were put on this gelatin film and incubated for 16 hrs at 37 degrees C. After staining with ponceau 3R dye, the digested area was evaluated under light microscopy. RESULTS: Digestion of gelatin was detected in more than 90%of breast cancer specimens, although it varied in degree and area for each case. In most cases, the gelatinolytic activity was located within cancer nests, and was not detected in stromal cells surrounding cancer cells. The gelatinolytic activity was inhibited by 1,10-phenanthroline, an inhibitor of matrix metalloproteinases (MMPs). CONCLUSIONS: In this study, the localization of net MMP activity was confirmed in breast cancer nest using film in situ zymography. Detailed analysis on the relationship between the strength or distribution of MMP activity and malignancy are anticipated in the future.

Azo Compounds↗

PubMed2001

Expression of fas/fas ligand (fasL) and its involvement in infiltrating lymphocytes in hepatocellular carcinoma (HCC).

BACKGROUND: This study was conducted to examine the expression of Fas/Fas ligand (FasL), to elucidate its relationship with tumor-infiltrating lymphocytes (TILs), and to detect possible gene mutation of Fas/FasL in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). METHODS: Indirect immunohistochemical staining was performed on formalin-fixed, paraffin-embedded sections of liver biopsy and surgery specimens from five normal livers, and from the livers of 30 patients with HCC. Fas/FasL mRNA-expressing cells and apoptotic cells were detected by in situ hybridization and DNA nick end labeling (TUNEL), respectively. We also performed polymerase chain reaction (PCR)-amplifying and direct sequencing for the Fas/FasL gene. RESULTS: Fas/FasL and its mRNA were localized on the membrane or in the cytoplasm in some HCC cells, as well as hepatocytes. Their expression was enhanced in areas with infiltrating inflammatory cells in the noncancerous regions of liver tissue and on the margins of the cancerous tissue. The positivity rate for TUNEL was elevated along these margins. The labeling index of Fas/FasL was lower in the cancerous liver tissue than in the surrounding noncancerous region (P < 0.01), and tended to decrease in proportion to the malignancy of tumor cells; Fas/FasL expression was not found on poorly differentiated type cancer cells. Fas(-)/FasL(+), FasL-mRNA(+) HCC cells were seen in one specimen of moderately differentiated type. Some CD8+T lymphocytes were TUNEL-positive around the cancerous region. In this study, cancerous and noncancerous tissues in HCC revealed no genetic mutations in any exons of Fas/FasL. CONCLUSIONS: These findings suggest that Fas/FasL expression was decreased in proportion to the malignancy of tumor cells, and that infiltrating CD8+ T lymphocytes play a role in apoptosis in HCC. The apoptosis in HCC could be regulated by the suppression of Fas/FasL expression, or, sometimes, by the enhancement of FasL expression.

Aged↗

PubMed2001

Telomerase activity levels for evaluating the surgical margin in breast-conserving surgery.

To evaluate the efficiency of measuring telomerase activity levels in clinical diagnosis, we performed a semiquantitative analysis of telomerase activity in breast tumors and compared the results with the histological findings. Breast tissue adjacent to areas of cancer were also serially resected and checked for telomerase activity. The amount of telomerase activity in the breast cancers ranged widely, from 0.36 to 1180 units/microg, with 31 of the 34 (91.2%) showing a value above 1.0unit/microg. None of the normal breast tissues including mastopathy, and only 4 (23.5%) of 17 benign breast masses had values above 1.0unit/microg. Telomerase activity was detectable in serial sections of adjacent tissues as far as 10mm from the macroscopic tumor margin with histologically detectable cancer cells. Furthermore, telomerase activity was detectable in the scrape specimens obtained from the stump of the surgical margins for breast-conserving surgery, and this activity was in accordance with the histological findings. These findings show that conducting a semiquantitative assay of telomerase activity is useful for evaluating the surgical margin in breast-conserving surgery.

Biomarkers, Tumor↗

PubMed2001

Increased matrix metalloproteinase 9 activity and mRNA expression in lung ischemia-reperfusion injury.

OBJECTIVES: In lung ischemia-reperfusion injury, neutrophil migration from the vasculature to the interstitial spaces plays a major role in tissue injury. Degradation of the basement membrane, which is composed of extracellular matrix (ECM) molecules, is necessary for neutrophil migration. Matrix metalloproteinases (MMPs) might play a role in ECM degradation in lung ischemia-reperfusion injury. We evaluated the changes in the activity of MMP-2 and MMP-9, and tissue inhibitor of metalloproteinase 1 (TIMP-1) gene expressions using rat lung transplantation models. METHODS: We divided animals into 4 groups. Groups I and II served as control groups with intact lungs (Group I) and 24-hour cold-preserved lungs (Group II). Groups III and IV received lung grafts after 24-hour cold preservation. The recipient animals were sacrificed 1 hour (Group III) or 24 hours (Group IV) after transplantation. We evaluated lung injury histologically. We assessed MMP activity using zymography. We assessed MMP-2, MMP-9, and TIMP-1 gene expression using biplex reverse transcriptase-polymerase chain reaction method. RESULTS: In Groups III and IV, we noted severe ischemia-reperfusion injury. We noted no significant difference in enzyme activity and gene expression of MMP-2 between Groups I and IV. The MMP-9 activity and gene expression were low during ischemia and increased on reperfusion. TIMP-1 gene expression was low during ischemia and at the early phase of reperfusion, and showed a dramatic increase at the late phase of reperfusion. CONCLUSIONS: Matrix metalloproteinase 9, but not MMP-2, may play an important role in ischemia-reperfusion injury. TIMP-1 increases at the late phase of reperfusion and may compensate for the activity of MMP-9.

Animals↗

PubMed2000

Loss of heterozygosity and microsatellite instability in ductal carcinoma in situ of the breast.

To investigate the alterations of genetic instabilities in carcinogenesis of the breast, we analyzed the allelotypic profile of 65 ductal carcinomas in situ (DCIS), compared with that of 207 invasive ductal carcinomas (IDC) of the breast. These studies were performed by means of examining microsatellite-length polymorphisms at seven loci (AluVpa, ESR, D11S988, D13S267, D16S398, D17S1159, and D17S855) from microdissected paraffin sections. Allelic loss or imbalance, considered a loss of heterozygosity (LOH), tended to be more frequently seen in IDC than in DCIS. In particular, the frequency of LOH at the 17p locus was significantly higher in IDC than in DCIS (42 vs. 23%, P=0.022). LOH in DCIS was most frequently seen at D16S398 (26%). LOH frequency at D16S398 in low- and intermediate-grade DCIS was higher than that in high-grade DCIS, while LOH frequencies at D11S988 and D17S1159 in low- and intermediate-grade DCIS was lower than those in high-grade DCIS. LOH frequency at D11S988 in non-comedo type DCIS was lower than that in comedo type DCIS. Furthermore, the frequency of microsatellite instability (MSI) at only one locus in DCIS (28%) was statistically higher than that in IDC (6%) (P<0.001), while there was no difference between the frequency of MSI at multiple loci in DCIS (6%) and that in IDC (3%). Together, these observations indicate that chromosomal losses of 16q may occur in low- and intermediate-grade DCIS and those of 11p and 17p may occur high-grade DCIS, and that MSI occurring at only one locus is not yet clear and MSI at multiple loci is uncommon in not only IDC but also DCIS of the breast.

Adult↗

PubMed2000

Expression of estrogen receptor alpha exon 5 and 7 deletion variant in human breast cancers.

BACKGROUND: An exon deletion variant of estrogen receptor (ER) mRNA has been reported, as one of the possible mechanisms of loss of ER function. METHODS: We examined the expression of exons 3, 5, and 7 in ER alpha mRNA and the frequency of exon deletion variant expression in 64 cases of human breast cancers and in 8 non-cancerous breast tissues using reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Approximately the same amount of wild-type (wt) mRNA was detected in all the non-cancerous breast tissues. In cancers, expression of wild-type exon 3 (w3), exon 5 (w5), and exon 7 (w7) was detected in 93.5%, 93.5%, and 91.3% of ER alpha protein (pER) positive cases, respectively, and 27.8%, 38.9%, and 44.4% in negative cases, respectively (p < 0.0001, p = 0.0035, and p = 0.0002). Although the variants for exon 5 (d5) and 7 (d7) were detected in both non-cancerous and cancerous tissues respectively, the variant for exon 3 was not detected at all. Comparatively, the ratio of d5/w5 was significantly higher in pER positive and progesterone receptor protein (pPgR) negative cases. CONCLUSIONS: We suspect that the exon 5 deletion does not work as a dominant positive.

Breast↗

PubMed2000

Comparison of five different antibodies in the immunohistochemical assay of estrogen receptor alpha in human breast cancer.

BACKGROUND: Estrogen receptor alpha (ER) expression is the best prognostic and predictive factor of hormone dependency of human breast cancers. Unlike enzyme immunoassay (EIA), which has been widely used to evaluate ER status in breast cancer, immunohistochemical assay (IHC) can detect ER in a small amounts of tissue with detailed localization. Although there is a sufficient number of ER antibodies against various regions of the protein, the reliability of IHC staining is only well understood for a few. IHC and EIA for the evaluation of the ER status of human breast cancer, therefore, should be compared using the same breast cancer tissues. METHODS: Five different ER antibodies (1D-5, C-314, G-20, C-311 and HC-20) that identify different amino acid sequences were used. The evaluation of ER status by IHC using these antibodies was compared with EIA concomitantly in 97 primary human breast cancer tissues RESULTS: The positivity rate for EIA was 68%. That of IHC for antibodies 1D-5, C-314, G-20, C-311 and HC-20 was 50.5%, 47.4%, 46.4%, 44.3% and 57.7%, respectively. The concordance between EIA was 76.3% for 1D-5 and 77.3% for HC-20, which is statistically highly significant (p<0.0001); Other antibodies were not. CONCLUSIONS: HC-20 is most suitable in the evaluation of the ER status of human breast cancers using the IHC method. Although antibody 1D-5 is also available, C-314, G20 and C-311 are unreliable in such an evaluation.

Antibodies↗

PubMed2000

Readministration of tamoxifen after adjuvant therapy for recurrent breast cancer.

BACKGROUND: Previous series concerning tamoxifen (TAM) rechallenge did not obtain satisfactory results. Using stricter criteria, we now assess the usefulness of readministration of TAM as an initial therapy for patients with recurrent breast cancer. METHOD: The eligibility criteria were postmenopausal, estrogen receptor (ER) positive or unknown, at least 12 months of adjuvant TAM, a 6-month or longer drug-free period and no previous therapy after recurrence. A total of 10 patients were enrolled. TAM was administered in daily doses of 20 or 30 mg. RESULTS: The mean age of the patients at the time of recurrence was 64.8 years. The receptor status was positive in 8 patients and unknown in 2. The median disease-free interval (DFI) after mastectomy was 71.7 months. A complete response was observed in one patient, a partial response in 6, stable disease in 2, and progression in one. The response rate was thus 70%, with an additional two patients showing no progression over 6 months. Although only one patient with a DFI of less than 48 months showed a positive response, all patients with a DFI longer than 48 months showed a clinical response. The duration of response was less than 12 months in 3 patients and longer in 4. CONCLUSION: The post-adjuvant readministration of tamoxifen is a useful first choice therapy for postmenopausal recurrent breast cancer patients with positive ER and longer DFI.

Aged↗

PubMed2000

Expression of the HB9 homeobox gene concomitant with proliferation accompanying epidermal stratification during development of chick embryonic tarsometatarsal skin.

A homeobox gene, HB9, has been isolated from the tarsometatarsal skin of 13-day-old chick embryos using a degenerate RT-PCR-based screening method. In situ hybridization analysis revealed that, during development of chick embryonic skin, the HB9 gene was expressed in epidermal basal cells of the placodes, but not in those of interplacodes, and in the dermal cells under the placodes at 9 days before addition of an intermediate layer by proliferation of the basal cells in the placodes. With the onset of epidermal stratification, the direction of the basal cell mitosis changed, with the axis becoming vertical to the epidermal surface. Placodes and interplacodes form outer and inner scales, respectively, after they have elongated distally (Tanaka S, Kato Y (1983b) J Exp Zool 225: 271-283). During scale ridge elongation at 12-15 days, HB9 was strongly expressed in the epidermis of the outer scale face, where the cell proliferation is more active than in the epidermis of the inner scale face; hence, stratification of the outer scale face is more prominent than that of the inner scale face. After 16 days, when mitotic activity in the epidermal basal cells decreases and the thickness of the epidermis is maintained at a constant level, the HB9 expression decreases with the onset of epidermal keratinization. These results suggest that HB9 may be involved in the proliferation of the epidermal basal cells that accompanies epidermal stratification.

Animals↗