title: Effect of estrogen sulfation by SULT1E1 and PAPSS on the development of estrogen-dependent cancers.
abstract: 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. SULT1E1 and PAPSS (PAPSS1 and PAPSS2) are responsible for the estrogen sulfation by providing catalyzing enzyme and universal sulfate donor. The present study showed the expression patterns of SULT1E1 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. SULT1E1 overexpression inhibited the tumorigenesis in subcutaneous xenograft model. By CCK-8 assay and flow cytometry assay, overexpression of SULT1E1 and PAPSS1 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 SULT1E1 and PAPSS1 suppressed cell growth and triggered apoptosis by downregulating the levels of c-myc, cyclin D1 and bcl-2, meanwhile, upregulating bax expression. In conclusion, the discrepancies in expressions of SULT1E1 and PAPSS between breast and endometrial tumorous tissues and their adjacent normal tissues were prominent. Overexpression of SULT1E1 and PAPSS1 retarded MCF-7 cells growth in vivo and in vitro by arresting cell cycles and inducing apoptosis. Thus, targeting SULT1E1 and PAPSS expressions might be an important approach for estrogen-dependent cancers.
authors.affiliation: Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Xu
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Liu
authors.forename: Fenghua
authors.initials: F
authors.lastname: Guo
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Ning
authors.forename: Xiuling
authors.initials: X
authors.lastname: Zhi
authors.forename: Xinhong
authors.initials: X
authors.lastname: Wang
authors.forename: Sifeng
authors.initials: S
authors.lastname: Chen
authors.forename: Lianhua
authors.initials: L
authors.lastname: Yin
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019938:Cyclin D1 / Q000096:biosynthesis; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D013430:Sulfate Adenylyltransferase / Q000235:genetics / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D014183:Transplantation, Heterologous; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D004967:Estrogens; C489427:MYC protein, human; D009097:Multienzyme Complexes; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D006861:Hydrogen Peroxide; C022322:PAPS synthetase; D013430:Sulfate Adenylyltransferase; D015238:Sulfotransferases; C020122:estrone sulfotransferase