Open AccessExpression of MAS 1 in breast cancer
Author(s) -
Luo Yi,
Tanabe Eriko,
Kitayoshi Misaho,
Nishiguchi Yukiko,
Fujiwara Rina,
Matsushima Sayako,
Sasaki Takamitsu,
Sasahira Tomonori,
Chihara Yoshitomo,
Nakae Dai,
Fujii Kiyomu,
Ohmori Hitoshi,
Kuniyasu Hiroki
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12719
Subject(s) - breast cancer , cancer research , medicine , endocrinology , tamoxifen , epidermal growth factor , mammary gland , receptor , cancer , biology
MAS 1 is a receptor for angiotensin 1‐7 (A1‐7), which is derived from angiotensin II (A‐ II ) by the action of angiotensin converting enzyme ( ACE ) 2. MAS 1 induces anti‐A‐ II phenotypes, such as vessel dilation and depression of blood pressure. Using immunohistochemistry, we examined the role of MAS 1 in 132 cases of invasive ductal carcinoma ( IDC ) of the breast. While benign mammary tissues expressed MAS 1 at high levels, MAS 1 expression was attenuated in all IDC , especially in scirrhous IDC . The decrease in MAS 1 expression was associated with tumor growth, lymph node metastasis, and grade. MAS 1 expression was inversely associated with the proliferation index and epidermal growth factor receptor and human epidermal growth factor receptor‐2 expression. Of the 132 cases, 12 (9.1%) were triple‐negative breast cancer ( TNBC ) cases. All TNBC cases (the 12 cases and the additional 36 cases using a tissue array) expressed MAS 1. Using the TNBC cell lines 4T1 and MDA ‐ MB ‐468, which expresses MAS 1, we found that cell growth, anti‐apoptotic survival and invasion were suppressed by MAS 1 activation with A1‐7 treatment and enhanced by MAS 1 knockdown. In contrast, synergic effect was found between tamoxifen and A1‐7 in a luminal A breast cancer cell line, MCF ‐7. Combination treatment with cisplatin, an ACE 2 activator, and an A‐ II type 1 receptor blocker showed synergic effects on tumor growth inhibition of 4T1 tumors in a syngeneic mouse model. These findings suggest that MAS 1 might act as an inhibitory regulator of breast cancer and may be a possible molecular target for this malignancy.