Open AccessEffect of estrogen sulfation by SULT 1 E 1 and PAPSS on the development of estrogen‐dependent cancers
Author(s) -
Xu Yali,
Liu Xiaoxia,
Guo Fenghua,
Ning Yanxia,
Zhi Xiuling,
Wang Xinhong,
Chen Sifeng,
Yin Lianhua,
Li Xiaobo
Publication year - 2012
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/j.1349-7006.2012.02258.x
Subject(s) - sulfation , estrogen , cell growth , carcinogenesis , cancer research , apoptosis , estrogen receptor , cyclin d1 , flow cytometry , biology , chemistry , cell , cell cycle , microbiology and biotechnology , cancer , biochemistry , endocrinology , breast cancer , gene , genetics
Estrogens are involved in the complex regulation of cell proliferation and apoptosis of hormone sensitive tumors including breast and endometrial cancers. Sulfation is the main pathway for estrogen metabolism, which is believed to be involved in the inactivation of estrogens in target tissues. SULT 1 E 1 and PAPSS ( PAPSS 1 and PAPSS 2) are responsible for the estrogen sulfation by providing catalyzing enzyme and universal sulfate donor. The present study showed the expression patterns of SULT 1 E 1 and PAPSS in the breast and endometrial tissues by tissue array analysis and the assessment of clinical samples. The estrogen sulfation enzymes were comparatively higher in the tumorous tissues than their adjacent normal tissues. SULT 1 E 1 overexpression inhibited the tumorigenesis in subcutaneous xenograft model. By CCK ‐8 assay and flow cytometry assay, overexpression of SULT 1 E 1 and PAPSS 1 by adenovirus blocked the estrogen pro‐proliferating effect and promoted cell apoptosis induced by H 2 O 2 in MCF ‐7 cells. By real‐time reverse transcription‐polymerase chain reaction and western‐blot assays, overexpression of SULT 1 E 1 and PAPSS 1 suppressed cell growth and triggered apoptosis by downregulating the levels of c‐myc, cyclin D 1 and bcl‐2, meanwhile, upregulating bax expression. In conclusion, the discrepancies in expressions of SULT 1E1 and PAPSS between breast and endometrial tumorous tissues and their adjacent normal tissues were prominent. Overexpression of SULT 1 E 1 and PAPSS 1 retarded MCF ‐7 cells growth in vivo and in vitro by arresting cell cycles and inducing apoptosis. Thus, targeting SULT 1 E 1 and PAPSS expressions might be an important approach for estrogen‐dependent cancers. ( Cancer Sci 2012; 103: 1000–1009)