Aromatase excess in cancers of breast, endometrium and ovary

Bulun S. E., Chen D., Lu M., Zhao H., Cheng Y., Demura M., ...Daha Fazla

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, cilt.106, ss.81-96, 2007 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 106
  • Basım Tarihi: 2007
  • Doi Numarası: 10.1016/j.jsbmb.2007.05.027
  • Dergi Adı: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.81-96
  • Anahtar Kelimeler: 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, POLYMERASE CHAIN-REACTION, ALTERNATIVELY SPLICED TRANSCRIPTS, CYTOCHROME-P450 CYP19 GENE, MESSENGER-RIBONUCLEIC-ACID, GYNECOLOGIC-ONCOLOGY-GROUP, HUMAN ADIPOSE-TISSUE, PHASE-II TRIAL, ESTROGEN-RECEPTOR EXPRESSION, NECROSIS-FACTOR RECEPTORS, ACUTE REGULATORY PROTEIN
  • Çukurova Üniversitesi Adresli: Hayır

Özet

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. (C) 2007 Elsevier Ltd. All rights reserved.