Androgen receptor gene mutation in male breast cancer

Lobaccaro, Jean‐Marc; Lumbroso, Serge; Belon, Charles; Galtier-Dereure, F.; Bringer, J.; Lesimple, Thierry; Namer, M.; Cutull, Bruno F.; Pujol, H; Sultan, Charles

doi:10.1093/hmg/2.11.1799

Cited by 118 publications

(43 citation statements)

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“…The single highest incidence of LOH is found at the AR locus for both borderline and invasive ovarian tumors, thus making AR a likely candidate gene. The only reported role of the androgen receptor in cancer is in the hormonal response of prostate cancer and male breast cancer (Schoenberg et al, 1994;Newmark et al, 1992;Lobaccaro et al, 1993;Tilley et al, 1996;Taplin et al, 1995). Ampli®cation of the androgen receptor gene has been found in recurrent hormone-refractory prostate tumors, but not in primary prostate tumors (Visakorpi et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

A one centimorgan deletion unit on chromosome Xq12 is commonly lost in borderline and invasive epithelial ovarian tumors

et al. 1998

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We have used polymerase chain reaction (PCR) ampli®cation of tandem repeats to study the pattern of allelic loss on chromosome X11.2-q12 in borderline and invasive epithelial ovarian tumors. Using eight microsatellite markers spanning Xq11.2-q12, 41 borderline and 65 invasive ovarian tumors, together with their corresponding normal tissues, were analysed. The highest percentage of loss of heterozygosity (LOH) was observed at the DXS1194 locus in borderline tumors (four of 16 informative cases, 25%) and at the androgen receptor (AR) locus in invasive epithelial ovarian tumors (18 of 47 informative cases, 38%). X chromosome activation studies performed in cases with LOH at the AR locus showed that the allelic loss at the AR locus is not con®ned to the inactive allele. A one centimorgan region including the AR locus and¯anked by the primers DXS1161 and PGK1P1 was identi®ed as the smallest common loss region in both borderline and invasive epithelial ovarian tumors.

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Section: Discussionmentioning

confidence: 99%

A one centimorgan deletion unit on chromosome Xq12 is commonly lost in borderline and invasive epithelial ovarian tumors

et al. 1998

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“…One year later, a point mutation in exon 3 was detected after screening 13 MBC patients for the presence of germline mutations in exons encoding the DNA-binding domain [19]. Again, the patient whose tumor carried this AR mutation presented a partial androgen insensitivity syndrome.…”

Section: Ar In Mbc: Genomicsmentioning

confidence: 99%

“…The logic behind this was a mutationally-induced decreased activity of AR that nullifies the protective effects of androgens on the male breast. Conversely, it has also been postulated that mutant AR forms might have altered interactions with partner proteins without defective DNA binding ability [20], or that AR mutants gain an altered sequence-specific DNA binding, enabling them to bind to estrogen response elements (EREs) and then promoting the transcription of estrogen-regulated genes [18,19]. In an endocrine background of elevated estrogen-androgen ratio, like in the case of aged males in whom 17b-estradiol levels are higher than in postmenopausal females [21], this abnormal DNA binding pattern may therefore promote MBC.…”

Section: Ar In Mbc: Genomicsmentioning

confidence: 99%

Androgen receptor and antiandrogen therapy in male breast cancer

et al. 2015

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Cancers arising in the male breast are uncommon. Male breast cancer is a hormone-driven disease that often expresses the estrogen receptor, and antiestrogen therapy represents the mainstay of treatment. Paradoxically, the advent of a wave of antiestrogens eclipsed the therapeutic potential of alternative therapeutic options. At the beginning of the hormonal therapy era the administration of antiandrogens to metastatic male breast cancer patients was proposed. Ever since the use of these compounds has largely been neglected. A therapeutic role for antiandrogens has been envisioned again in recent years. First, molecular characterization efforts pointed to the androgen receptor as a potential therapeutic target. Second, the development of aromatase inhibitors unexpectedly raised the need for neutralizing androgens in order to tackle endocrine feedback mechanisms responsible for acquired resistance. We herein provide an overview of molecular studies where the androgen receptor was investigated at the genomic, transcriptomic or phenotypic level. We then discuss androgens in the context of the endocrine networks nourishing male breast cancer. Finally, clinical evidence on antiandrogens is summarized along with strategies should be implemented to improve the medical management of these patients.

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“…Finally, we studied the integrity of the androgen receptor gene in 10 tumors excised from 8 advancedstage cases of EMPD, because mutations of the androgen receptor gene may confer a growth advantage in prostate cancer (Gaddipati et al, 1994;Newmark et al, 1992;Taplin et al, 1995;Tilley et al, 1996) as well as in male breast cancer (Lobaccaro et al, 1993). Exons 2 to 8 of the androgen receptor gene were directly sequenced.…”

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confidence: 99%

Expression of Structurally Unaltered Androgen Receptor in Extramammary Paget's Disease

Fujimoto

Takata

Hatta

et al. 2000

Laboratory Investigation

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SUMMARY: Extramammary Paget's disease (EMPD) is an uncommon neoplasm of the skin that shows differentiation to an apocrine sweat gland. Although we previously showed that erbB-2 overexpression may play a part in the progression of EMPD, molecular genetic defects underlying the development of EMPD are poorly understood. In the study described here, we examined androgen receptor expression and gene alterations in 30 cases of EMPD without internal malignancy. Immunohistochemistry revealed that 24 of 30 (80%) cases of EMPD variably expressed nuclear androgen receptor. Semi-quantitation of receptor content by scoring immunostained sections showed no difference between in situ (n ϭ 17) and invasive (n ϭ 13) EMPD tumors. Androgen receptor expression was also observed in four of six lymph node metastases. In these lymph nodes, expression of androgen receptor mRNA was confirmed by reverse transcriptase-polymerase chain reaction. Direct sequencing of exon 2 through exon 8, which encodes DNA-and hormone-binding domains of the androgen receptor gene, revealed no mutation in any of the 10 advanced stage tumors. Neither amplification nor deletion of the androgen receptor gene locus was detected by dual color fluorescence in situ hybridization analysis in 14 tumors. The present findings showing frequent expression of structurally unaltered androgen receptor in an advanced stage of EMPD may provide a rational basis for hormone therapy, which is widely used in the treatment of metastatic prostate cancer and androgen receptor-positive breast cancer recurrence. (Lab Invest 2000, 80:1465-1471.E xtramammary Paget's disease (EMPD) is an uncommon neoplasm of apocrine gland-bearing skin, that most commonly involves the vulvar, perianal, perineal, scrotal, and penile regions (Heymann, 1993). Although it is rarely associated with underlying adenocarcinoma, it mostly begins as an intraepidermal adenocarcinoma that can invade the dermis and may metastasize via the lymphatic system (Feuer et al, 1990;Hart and Millman, 1977;Jones et al, 1979;Murata et al, 1999). The histogenesis of EMPD has long been disputed. Emerging information, however, supports the concepts that Paget's cells in EMPD are of glandular origin, usually showing apocrine differentiation and that the disease may arise from a pluripotential epidermal precursor (Guarner et al, 1989;Mazoujian et al, 1984;Roth et al, 1977).The molecular genetic defects underlying EMPD are poorly understood. We previously showed that erbB-2 overexpression by either gene amplification or transcriptional activation may play a part in the progression of EMPD (Takata et al, 1999). However, other molecular genetic defects, including p53 mutations, allelic loss of several selected chromosome arms as well as abnormal activation of the ␤-catenin gene, which are commonly seen in other epithelial malignancies, were not detected in EMPD (Takata et al, 1999;Takata et al, 1997). To explore further the molecular pathogenesis of EMPD, we aimed at examining androgen receptor expression in Paget's cells of EMPD f...

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Androgen receptor gene mutation in male breast cancer

Cited by 118 publications

References 0 publications

A one centimorgan deletion unit on chromosome Xq12 is commonly lost in borderline and invasive epithelial ovarian tumors

A one centimorgan deletion unit on chromosome Xq12 is commonly lost in borderline and invasive epithelial ovarian tumors

Androgen receptor and antiandrogen therapy in male breast cancer

Expression of Structurally Unaltered Androgen Receptor in Extramammary Paget's Disease

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