BRCA1 and BRCA2 mRNA levels are coordinately elevated in human breast cancer cells in response to estrogen.
The steady state levels of BRCA1 and BRCA2 mRNAs were shown to be coordinately elevated by the steroid hormone estrogen but not progesterone in the human breast cancer cell lines BT-483 and MCF-7. Two different antiestrogens, trans 4'-hydroxytamoxifen and ICI 182,780, blocked the elevation of BRCA1 and BRCA2 mRNA levels, confirming that the effect was mediated through the estrogen receptor. In BT-483 cells, BRCA1 and BRCA2 mRNA levels were both elevated 18 to 24 h after estrogen stimulation, suggesting that the effect of estrogen was indirect. Cycloheximide blocked the estrogen effect implying that estrogen induces synthesis of an unidentified estrogen-responsive protein(s) that then result in the elevation of BRCA1 and BRCA2 mRNAs.
Department of Pediatrics and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas 75235-8591, USA.
M A
MA
Spillman
A M
AM
Bowcock
D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics* / Q000503:physiopathology; D003513:Cycloheximide / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D004965:Estrogen Antagonists; D004967:Estrogens; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D003513:Cycloheximide