Identification of an exon 3 deletion splice variant androgen receptor mRNA in human breast cancer

Zhu, Xiang; Daffada, Angela A.I.; Chan, Christina M.W.; Dowsett, Mitchell

doi:10.1002/(sici)1097-0215(19970807)72:4<574::aid-ijc4>3.0.co;2-n

Cited by 61 publications

(20 citation statements)

References 33 publications

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“…It has been reported to be involved in differentiation and growth of normal breast cells 23,24. Szelei et al25 have distinguished 3 mechanisms of androgen control of cellular balance: proliferation stimulation, proliferation inhibition, and apoptosis inhibition.…”

Section: Discussionmentioning

confidence: 99%

Expression of Androgen Receptor in Estrogen Receptor–positive Breast Cancer

Agrawal¹,

Ziółkowski²,

Grzebieniak³

et al. 2016

Applied Immunohistochemistry &Amp; Molecular Morphology

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Objectives:The aim of the study was to estimate the implications of androgen receptor (AR) expression in estrogen receptor (ER)-positive subset of invasive breast carcinoma patients.Patients and Methods:We assessed the AR expression in a subset of 96 predominantly ER-positive invasive breast carcinomas and correlated this expression pattern with several clinical and pathologic parameters: histologic type and grade, tumor size, lymph node status, progesterone receptor (PgR) status, and human epidermal growth factor receptor type 2 (HER2) overexpression and evaluated the association of these parameters with 10-year survival using univariate and multivariate analyses. Data used for analysis were derived from medical records. Immunohistochemical analysis for AR, ER, PgR, and HER2 were carried out and semiquantitative evaluation of stainings was performed.Results:AR expression was demonstrated in 43.7% of patients. AR was significantly related to well-differentiated tumors and positive PgR/HER2 status. No statistical difference was demonstrated in AR expression in relation to tumor size, lymph node status, menopausal status, and tumor histologic type. AR expression was not an independent prognostic factor related to 10-year survival in ER-positive cancers. In multivariate analyses, older age at diagnosis, larger tumor size, and positive lymph node status were significantly associated with poorer 10-year survival.Conclusions:AR expression is significantly associated with ER/PgR/HER2 status and positively related to well-differentiated tumors. Although AR status in ER-positive cancers is not an independent prognostic factor, it might provide important additional information on prognosis and become a promising object for targeted therapy.

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Section: Discussionmentioning

confidence: 99%

Expression of Androgen Receptor in Estrogen Receptor–positive Breast Cancer

Agrawal¹,

Ziółkowski²,

Grzebieniak³

et al. 2016

Applied Immunohistochemistry &Amp; Molecular Morphology

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“…16 17 Both short and long AR CAG repeats have been associated with breast cancer development. 12 13 Yu et al 12 found that shorter CAG repeat length was associated with more aggressive forms of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

High frequency of skewed X inactivation in young breast cancer patients

Kristiansen

Langerød²,

Knudsen

et al. 2002

Journal of Medical Genetics

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Introduction: Patients with invasive ovarian cancer were recently shown to have a higher frequency of skewed X chromosome inactivation in peripheral blood cells compared to patients with borderline cancer and controls. In this study, we analysed the X inactivation pattern in peripheral blood from 216 breast cancer patients. Methods: X inactivation analysis was performed using HpaII predigestion of DNA followed by PCR of the highly polymorphic CAG repeat of the androgen receptor gene (AR), which amplifies the undigested inactive X chromosome only. The X inactivation pattern was classified as skewed when 90% or more of the cells preferentially used one X chromosome. Results: Young breast cancer patients (27-45 years) had a higher frequency of skewed X inactivation than young controls (13 and 1%, respectively) (p=0.009), whereas no difference was found for middle aged and older patients compared to controls of a similar age. Conclusions: A germline mutation in an X linked tumour suppressor gene may give a proliferative advantage to cells with this mutation on the active X chromosome, thus causing skewed X inactivation and an increased risk for developing cancer. Another possible explanation could be that females with a constitutionally skewed X inactivation pattern are more susceptible to develop breast cancer because of an X linked low penetrance susceptibility allele that is affected by the inactivation pattern.

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“…Even within this normal range, CAG repeat number is inversely associated with AR-mediated transcriptional activation in vitro [1,2]. Involvement of the AR in breast tumourigenesis is suggested by the existence of inactivating germline mutations in the hormone-binding domain in male breast cancer patients [3,4], and by splice variants that disrupt the transactivation domain in female breast tumours and tumour cell lines [5]. …”

Section: Introductionmentioning

confidence: 99%