Open AccessAmyloid precursor protein in human breast cancer: An androgen‐induced gene associated with cell proliferation
Author(s) -
Takagi Kiyoshi,
Ito Shigehiro,
Miyazaki Toshiaki,
Miki Yasuhiro,
Shibahara Yukiko,
Ishida Takanori,
Watanabe Mika,
Inoue Satoshi,
Sasano Hironobu,
Suzuki Takashi
Publication year - 2013
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.12239
Subject(s) - androgen receptor , immunohistochemistry , breast carcinoma , androgen , estrogen receptor , cancer research , estrogen , medicine , breast cancer , endocrinology , dihydrotestosterone , carcinoma , biology , cancer , hormone , prostate cancer
Amyloid precursor protein ( APP ) is a transmembrane protein that is highly expressed in brain tissue. Recently, APP has been implicated in some human malignancies, and its regulation by androgens has also been demonstrated. Such findings suggest the importance of APP in hormone‐dependent breast carcinoma, but APP has not yet been examined in breast carcinoma tissues. Therefore, in this study, we examined the biological and clinical significance of APP in breast carcinoma using immunohistochemistry and in vitro studies. APP immunoreactivity was detected in 57 out of 117 (49%) breast carcinoma tissues examined, and it was positively associated with androgen receptor ( AR ) expression. APP immunoreactivity was also significantly associated with K i‐67 LI and increased risk of recurrence in the estrogen receptor ( ER )‐positive cases, and was an independent prognostic factor in these patients. Subsequent in vitro experiments demonstrated that APP m RNA expression was significantly induced by biologically active androgen dihydrotestosterone in both a dose‐dependent and a time‐dependent manner in MCF ‐7 breast carcinoma cells, which was potently suppressed by an AR blocker hydroxyflutamide. Moreover, cell proliferation activity of MCF ‐7 and MDA ‐ MB ‐231 cells was significantly associated with their APP expression level. These findings suggest that APP is an androgen‐induced gene that promotes proliferation activity of breast carcinoma cells. Moreover, APP immunohistochemical status is considered a potent prognostic factor in ER ‐positive breast cancer patients.