Long CAG Repeat Sequence and Protein Expression of Androgen Receptor Considered as Prognostic Indicators in Male Breast Carcinoma

Song, Yanni; Geng, Jiao; Liu, Tong; Zhong, Zhenbin; Liu, Yang; Xia, Bo; Ji, Hongfei; Li, Xiaomei; Zhang, Guoqiang; Ren, Yanlv; Li, Zhigao; Pang, Da

doi:10.1371/journal.pone.0052271

Cited by 17 publications

(13 citation statements)

References 14 publications

(23 reference statements)

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“…Conversely, the evaluation of sex hormone receptor status in a series of 39 patients suggested that 5-year diseasefree survival and overall survival were significantly shorter for patients with AR-positive tumors [44], as analogously noted in a cohort examining 102 MBC patients where AR-expressing MBC patients apparently derived a lower benefit from tamoxifen [45]. An association between AR expression and longer CAG repeats was also reported negatively impacting survival outcomes [27]. Conversely, in one of the largest series presented so far AR-positive luminal A MBC had improved overall survival compared with matched FBC cases [46].…”

Section: Ar In Mbc: Expression Levels and Clinical Outcomesmentioning

confidence: 84%

“…Two studies searching for an association between CAG repeat length and MBC did not notice any appreciable differences between cases and the respective control groups [22,25]. Two other studies suggested that longer CAG repeats are more common in MBC that in controls [26,27], and a trend toward a higher frequency of shorter CAG tracts in the control group emerged from a fifth report [28]. Thus, even though genetic evidence is scarce and somewhat ambiguous, the scenario proposed is that androgen hyposensitivity caused by either AR mutations or long CAG repeats might be a causal factor for MBC.…”

Section: Ar In Mbc: Genomicsmentioning

confidence: 99%

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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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Section: Ar In Mbc: Expression Levels and Clinical Outcomesmentioning

confidence: 84%

Section: Ar In Mbc: Genomicsmentioning

confidence: 99%

Androgen receptor and antiandrogen therapy in male breast cancer

et al. 2015

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“…For example, the androgen signal provides a mitogenic effect in the prostate, where decreasing CAG repeat length of the AR gene increases the cancer risk. By contrast, androgens in breast tissues function in an antimitogenic response, in which long CAG repeats indicated a higher risk for male (14) and female (15) patients with breast cancer. Finally, we observed that the colorectal cancer group had a longer CAG repeat length compared with the control group.…”

Section: Discussionmentioning

confidence: 99%

“…AR-Forward was fluorescently labeled with 6-carboxyfluorescine (FAM). PCR was carried out as we have previously described (14). Data were analyzed by GeneScan Software (Applied Biosystems) and Genetyper Software (Applied Biosystems).…”

Section: Pcr-based Genescan Analysis Of Ar Cag Repeats Lengthmentioning

confidence: 99%

Polymorphic CAG Repeat and Protein Expression of Androgen Receptor Gene in Colorectal Cancer

Huang

Wang

Song

et al. 2015

Molecular Cancer Therapeutics

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Although somatic alterations in CAG repeats in the androgen receptor (AR) gene have been suggested to predispose to colorectal cancer, less is known about AR in colorectal cancer carcinogenesis. Because of lack of relevant analysis on CAG repeat length and AR expression in colorectal cancer, we aimed to investigate the prognostic value of polymorphic CAG and protein expression of the AR gene in patients with colorectal cancer. A case-control study was carried out on 550 patients with colorectal cancer and 540 healthy controls to investigate whether polymorphic CAG within the AR gene is linked to increased risk for colorectal cancer. Polymorphic CAG and AR expression were analyzed to clarify their relationship with clinicopathologic and prognostic factors in patients with colorectal cancer. The study showed that the AR gene in patients with colorectal cancer had a longer CAG repeat sequence than those in the control group, as well as increased risk for colorectal cancer among females (P ¼ 0.013), males (P ¼ 0.002), and total colorectal cancer population (P < 0.001), respectively. AR expression exhibited a significant difference in long CAG repeat sequence among males (P < 0.001), females (P < 0.001), and total colorectal cancer study population (P < 0.001). Both long CAG repeat sequence and negative AR expression were associated with a short 5-year overall survival (OS) rate in colorectal cancer. Long CAG repeat sequences and the absence of AR expression were closely related to the development of colorectal cancer. Both long CAG and decreased AR expression were correlated with the poor 5-year OS in patients with colorectal cancer.

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“…Breast cancer tissue microarrays (TMA) were used as described previously [23, 24] and immunohistochemically stained for AR, ER, PR, Her2, Ki67 and β-catenin expression levels. Briefly, after deparaffinization, sections were hydrated and underwent Ethylene Diamine Tetraacetic Acid (EDTA) buffer (pH 8.0) or sodium citrate buffer (pH 6.0) retrieval.…”

Section: Methodsmentioning

confidence: 99%

Androgen Receptor Expression and Bicalutamide Antagonize Androgen Receptor Inhibit β-Catenin Transcription Complex in Estrogen Receptor-Negative Breast Cancer

Huang

Han

Liang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Little is known about the potential mechanism of action for androgen receptor (AR) targeting treatment in estrogen receptor (ER)-negative breast cancer. This study aimed to evaluate AR status and its prognosis in four breast cancer subtypes. Bicalutamide has been identified as an AR antagonist and used for treating AR+/ER- breast cancer in a phase II trial. Our studies will clarify its mechanism in breast cancer treatment. Methods: A total of 510 consecutive cases of invasive ductal cancer (IDC) were evaluated in this study. The expression of AR was analyzed by immunohistochemistry and compared with patient survival, and its implications were evaluated in four subtypes of IDC. We examined bicalutamide as an AR antagonist to inhibit proliferation and increased apoptosis in AR+/ER- breast cancer cell lines. We explored the tumor suppressive functions of bicalutamide in vitro and vivo and its related mechanisms in AR+/ER- breast cancer. Results: AR expression was related to that of ER (P<0.001), PR (P<0.001), Her2 (P=0.017), Ki-67(P=0.020) and to four subtypes (P<0.001). AR retained independent prognostic signifcance (P=0.007, ER- cases; P=0.001, ER+ cases; P=0.001, total cases). We found that bicalutamide significantly decreased viability and increased apoptosis in vitro and vivo. The mechanistic analysis revealed that bicalutamide blocked androgen-stimulated oncogenic AR and Wnt/β-catenin signaling and inhibited the growth of AR+/ER- breast cancer. Conclusion: Our studies provide novel insights into bicalutamide as an antagonist of AR function in AR+/ER- breast cancer and reveal the mechanistic basis for targeting AR as a therapeutic opportunity for patients with AR+/ER- breast cancer.

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Long CAG Repeat Sequence and Protein Expression of Androgen Receptor Considered as Prognostic Indicators in Male Breast Carcinoma

Cited by 17 publications

References 14 publications

Androgen receptor and antiandrogen therapy in male breast cancer

Androgen receptor and antiandrogen therapy in male breast cancer

Polymorphic CAG Repeat and Protein Expression of Androgen Receptor Gene in Colorectal Cancer

Androgen Receptor Expression and Bicalutamide Antagonize Androgen Receptor Inhibit β-Catenin Transcription Complex in Estrogen Receptor-Negative Breast Cancer

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