Androgen receptor status in female breast cancer: RT-PCR and Western blot studies

Bryś, Magdalena; Wójcik, Magdalena; Romanowicz-Makowska, Hanna; Krajewska, Wanda M.

doi:10.1007/s004320100294

Cited by 41 publications

(39 citation statements)

References 43 publications

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“…The effect of flutamide on maspin induction in breast cancer cells simulates that of androgen withdrawal in prostate cancer, because recent studies have identified maspin induction after androgen ablation and/or radical proctectomy (24). It is well documented that contrary to normal breast epithelial cells, breast cancer has a high level of androgen receptor (AR; also observed by us in the archival tissues tested), and the presence of this receptor is associated with high-grade and/or metastatic disease (25,26). By using reverse transcription-PCR analysis, we have also confirmed that MCF-7 cells have a high level of AR with no detectable levels in HMEC1331 cells.…”

Section: Discussionsupporting

confidence: 82%

Regulating the Tumor Suppressor Gene Maspin in Breast Cancer Cells

Khalkhali‐Ellis

Christian

Kirschmann

et al. 2004

Clinical Cancer Research

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Purpose: Mammary epithelial cells and the majority of breast cancer tumors require estrogen for continued growth. Antiestrogen therapy alone, or in combination with other drugs, has long been a common procedure for breast cancer treatment and prophylaxis. Thus, there is a critical need to elucidate the mechanism(s) of action of antiestrogen treatment, especially for patients who are at risk of breast cancer development or who are currently receiving hormone therapy. In this study, we examined the ability of hormones to regulate the expression of a tumor suppressor gene, maspin, which is a serine protease inhibitor (serpin) that plays an important role in mammary gland development and is silenced during breast cancer progression. Specifically, our hypothesis tested the clinical efficacy of tamoxifen to regulate maspin expression.Experimental Design: We used maspin promoter luciferase reporter plasmids that were transfected into normal human mammary epithelial (HMEC1331) and MCF-7 breast cancer cells, followed by determination of the effect of hormones and their antagonists on maspin promoter activity. At the protein level, cytosolic fractions from both cell types before and after hormone treatment were subjected to Western blot analysis to determine maspin level.Results and Conclusions: Our studies revealed that the antiestrogen tamoxifen induces maspin promoter activity. Interestingly, antiandrogen flutamide could also induce maspin in both cell lines tested. These observations were further confirmed in patient tissues. These novel findings provide a new mechanism of action for tamoxifen under normal and pathological conditions. More significantly, these findings could have a potential impact on future therapeutic intervention strategies for breast cancer.

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Section: Discussionsupporting

confidence: 82%

Regulating the Tumor Suppressor Gene Maspin in Breast Cancer Cells

Khalkhali‐Ellis

Christian

Kirschmann

et al. 2004

Clinical Cancer Research

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“…The number of AR-positive samples and the level of AR mRNA were significantly higher among the cancer samples than among normal samples. The expression level of both AR gene and AR protein in nuclei was found to be positively correlated with tumor invasiveness (Brys et al 2002). Our study showed that AR had a similar effect as ERα in the up-regulation of LRP16 transcription.…”

Section: Discussionsupporting

confidence: 58%

Up-regulation of LRP16 mRNA by 17beta-estradiol through activation of estrogen receptor alpha (ERalpha), but not ERbeta, and promotion of human breast cancer MCF-7 cell proliferation: a preliminary report.

Han¹,

Ym²,

Lü³

et al. 2003

Endocrine-Related Cancer

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LRP16 is a novel gene cloned from lymphocytic cells, and its function is not known. The expression level of LRP16 mRNA was up-regulated by estrogen in breast cancer MCF-7 cells based on the computed aided serial analysis of gene expression (SAGE) analysis. In this study, we investigate the effect of 17β-estradiol (17β-E 2 ) on the expression of LRP16 mRNA and the effects of overexpression of LRP16 on the proliferation of cultured MCF-7 cells and the possible mechanisms involved. The expression level of LRP16 mRNA induced by 17β-E 2 was determined by Northern blot analysis. LRP16 promoter-controlled luciferase expression vector (pGL3-S 0 ) was co-transfected with various nuclear receptors, including estrogen receptor α and β (ERα and ERβ), glucocorticoid receptor α (GRα), androgen receptor (AR) and peroxisome-proliferator activated receptor γ and α (PPARγ and PPARα) into COS-7 cells, and the relative luciferase activity was measured using Dual-luciferase report assay systems. The effect of overexpression of LRP16 on MCF-7 proliferation was examined by the Trypan Blue exclusion method, and the cell cycle was analyzed by flow cytometry. The expression levels of cyclin E, p53 and p21 WAF1/CIP1 proteins were determined by Western blot analysis. The results showed (1) 17β-E 2 induced a five-to eightfold increase in LRP16 mRNA levels in MCF-7 cells; (2) the relative luciferase activities in the COS-7 cells co-transfected by pGL3-S 0 and ERα or AR were 7.8-fold and 11-fold respectively of those in the control cells transfected by pGL3-S 0 alone; (3) overexpression of LRP16 stimulated MCF-7 cell proliferation, and the numbers of cells in the S-phase of the cell cycle in cells transfected with LRP16 increased about 10% compared with the control cells; and (4) cyclin E levels were much higher in cells with overexpression of LRP16 than in the control cells, while the expression levels of p53 and p21 WAF1/CIP1 were not different between the two groups of cells. From these results we concluded that estrogen up-regulates the expression level of LRP16 mRNA through activation of ERα and that overexpression of LRP16 promotes MCF-7 cell proliferation probably by increasing cyclin E.

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“…Some studies have focused on the pattern of AR expression in different histological subtypes of breast cancer but the majority of data refer only to ductal carcinomas [7,28]. A strong, consistent AR positivity has been described both in in situ and in invasive apocrine carcinomas as well as in apocrine metaplasia and the intense expression of ARs was often accompanied by a lack of ER and PR immunoreactivity; AR positivity was therefore proposed as a specific marker of apocrine differentiation [15].In one series of invasive breast carcinomas [21], in which ARs were examined, only 14 lobular carcinomas were included; most of these showed an intense AR immunoreactivity.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical study of androgen receptors in breast carcinoma. Evidence of their frequent expression in lobular carcinoma

et al. 2005

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Androgens and androgen receptors (AR) are involved in the pathogenesis of breast cancer. Epidemiological studies have shown a significant association between the risk of breast cancer and androgens. However, the functional role and clinical value of AR expression in breast carcinoma have still not been clearly defined. The present study was set up to investigate the prevalence of ARs in a series of consecutive invasive breast carcinomas (IBCs) and to evaluate the patterns of AR phenotypes in a series of selected invasive lobular carcinomas (ILCs). Among the 250 consecutive IBCs (consisting of 212 ductal and 38 lobular neoplasms), AR immunoreactivity was observed in 151/250 (60.4%) cases, being expressed in 118/212 (56%) ductal and 33/38 (87%) lobular carcinomas (a statistically significant difference, chi2=11.82). AR expression was frequently associated with ER (65.2%, chi2=14.33) and PR positivity (66.9%, chi2=7.36). Most AR positive cases showed a low proliferative index (63.7%) and a low or intermediate histological grade (G1-G2, 63.9%). Among the 80 selected ILCs, AR expression was observed in 64/80 (80%) cases. Our results confirm that ARs are expressed in most breast cancers. Moreover, we demonstrated that AR positivity is particularly marked in lobular neoplasms. In addition, AR positive carcinomas are frequently characterized by a low or intermediate grade, a low proliferative index and ER and/or PR co-expression.

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Androgen receptor status in female breast cancer: RT-PCR and Western blot studies

Abstract: The high incidence of AR expression in female breast tumours suggests a potential role of AR in breast cancer, in addition to OR and PR.

Cited by 41 publications

References 43 publications

Regulating the Tumor Suppressor Gene Maspin in Breast Cancer Cells

Regulating the Tumor Suppressor Gene Maspin in Breast Cancer Cells

Up-regulation of LRP16 mRNA by 17beta-estradiol through activation of estrogen receptor alpha (ERalpha), but not ERbeta, and promotion of human breast cancer MCF-7 cell proliferation: a preliminary report.

Immunohistochemical study of androgen receptors in breast carcinoma. Evidence of their frequent expression in lobular carcinoma

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