Aromatase excess in cancers of breast, endometrium and ovary

作者：Bulun Serdar E^*; Chen Dong; Lu Meiling; Zhao Hong; Cheng Youhong; Demura Masashi; Yilmaz Bertan; Martin Regina; Utsunomiya Hiroki; Thung Steven; Su Emily; Marsh Erica; Hakim Amy; Yin Ping; Ishikawa Hiroshi; Amin Sanober; Imir Gonca; Gurates Bilgin; Attar Erkut; Reierstad Scott; Innes Joy; Lin Zhihong

来源：Journal of Steroid Biochemistry and Molecular Biology, 2007, 106(1-5): 81-96.

DOI：10.1016/j.jsbmb.2007.05.027

• aromatase
• aromatase inhibitor
• breast cancer
• endometrial cancer
• endometriosis
• uterine leiomyomata
• fibroids
• aromatase overexpression
• gain-of-function mutations
• aromatase excess syndrome
• gynecomastia
• estrogen
• estrogen biosynthesis
• endometrium
• uterus

Pathogenesis and growth of three common women's cancers (breast, endometrium and ovary) are linked to estrogen. A single gene encodes the key enzyme for estrogen biosynthesis named aromatase, inhibition of which effectively eliminates estrogen production in the entire body. Aromatase inhibitors successfully treat breast cancer, whereas their roles in endometrial and ovarian cancers are less clear. Ovary, testis, adipose tissue, skin, hypothalamus and placenta express aromatase normally, whereas breast, endometrial and ovarian cancers overexpress aromatase and produce local estrogen exerting paracrine and intracrine effects. Tissue-specific promoters distributed over a 93-kb regulatory region upstream of a common coding region alternatively control aromatase expression. A distinct set of transcription factors regulates each promoter in a signaling pathway- and tissue-specific manner. In cancers of breast, endometrium and ovary, aromatase expression is primarly regulated by increased activity of the proximally located promoter I.3/II region. Promoters I.3 and 11 lie 215 bp from each other and are coordinately stimulated by PGE(2) via a cAMP-PKA-dependent pathway. In breast adipose fibroblasts exposed to PGE2 secreted by malignant epithelial cells, PKC is also activated, and this potentiates cAMP-PKA-dependent induction of aromatase. Thus, inflammatory substances such as PGE2 may play important roles in inducing local production of estrogen that promotes tumor growth.

• 出版日期2007-9
• 单位西北大学