Androgenic pathways in the progression of triple-negative breast carcinoma: a comparison between aggressive and non-aggressive subtypes

• Published in: Breast cancer research and treatment 2014-06, Vol.145 (2), p.281-293
• Main Authors: McNamara, Keely M., Yoda, Tomomi, Nurani, Alif Meem, Shibahara, Yukiko, Miki, Yasuhiro, Wang, Lin, Nakamura, Yasuhiro, Suzuki, Koyu, Yang, Yang, Abe, Eriko, Hirakawa, Hisashi, Suzuki, Takashi, Nemoto, Noriko, Miyashita, Minoru, Tamaki, Kentaro, Ishida, Takanori, Brown, Kristy A., Ohuchi, Noriaki, Sasano, Hironobu
• Format: Article
• Language: English
• Subjects: 3-Hydroxysteroid Dehydrogenases - genetics; 3-Hydroxysteroid Dehydrogenases - metabolism; Aldo-Keto Reductase Family 1 Member C3; Analysis; Androgens; Androgens - metabolism; Breast cancer; Cancer; Cancer research; Cancer therapies; Carcinoma; Carcinoma, Ductal, Breast - drug therapy; Carcinoma, Ductal, Breast - metabolism; Carcinoma, Ductal, Breast - pathology; Carcinoma, Intraductal, Noninfiltrating - drug therapy; Carcinoma, Intraductal, Noninfiltrating - metabolism; Carcinoma, Intraductal, Noninfiltrating - pathology; Cell Line, Tumor; Cell Proliferation; Cholestenone 5 alpha-Reductase - genetics; Cholestenone 5 alpha-Reductase - metabolism; Development and progression; Dihydrotestosterone - pharmacology; Enzymes; Female; Gene Expression Regulation, Neoplastic; Humans; Hydroxyprostaglandin Dehydrogenases - genetics; Hydroxyprostaglandin Dehydrogenases - metabolism; Immunohistochemistry; Keratin-5 - metabolism; Keratin-6 - metabolism; Medicine; Medicine & Public Health; Metabolism; Oncology; Pathology; Physiological aspects; Preclinical Study; Receptor, Epidermal Growth Factor - metabolism; Receptors, Androgen - metabolism; Steroids; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-014-2942-6

One of the active intracellular pathways/networks in triple-negative breast carcinoma (TNBC) is that of the androgen receptor (AR). In this study, we examined AR and androgen-metabolising enzyme immunoreactivity in subcategories of TNBC to further elucidate the roles of androgenic pathways in TNBC. We utilised formalin-fixed paraffin-embedded breast cancer samples from ductal carcinoma in situ (DCIS) and invasive ductal carcinoma patient cohorts. We then used immunohistochemistry to classify these samples into basal-like and non-basal samples and to assess interactions between AR, androgen-metabolising enzymes and proliferation. To further substantiate our hypothesis and provide mechanistic insights, we also looked at the expression and regulation of these factors in publically available microarray data and in a panel of TNBC AR-positive cell lines. DCIS was associated with higher levels of AR and enzymes ( p