Estrogen responsiveness of the TFIID subunit TAF4B in the normal mouse ovary and in ovarian tumors.
Estrogen signaling in the ovary is a fundamental component of normal ovarian function, and evidence also indicates that excessive estrogen is a risk factor for ovarian cancer. We have previously demonstrated that the gonadally enriched TFIID subunit TAF4B, a paralog of the general transcription factor TAF4A, is required for fertility in mice and for the proliferation of ovarian granulosa cells following hormonal stimulation. However, the relationship between TAF4B and estrogen signaling in the normal ovary or during ovarian tumor initiation and progression has yet to be defined. Herein, we show that Taf4b mRNA and TAF4B protein, but not Taf4a mRNA or TAF4A protein, are increased in whole ovaries and granulosa cells of the ovary after exposure to 17beta-estradiol or the synthetic estrogen diethylstilbestrol and that this response occurs within hours after stimulation. Furthermore, this increase occurs via nuclear estrogen receptors both in vivo and in a mouse granulosa cancer cell line, NT-1. We observe a significant increase in Taf4b mRNA in estrogen-supplemented mouse ovarian tumors, which correlates with diminished survival of these mice. These data highlight the novel response of the general transcription factor TAF4B to estrogen in the normal ovary and during ovarian tumor progression in the mouse, suggesting its potential role in regulating actions downstream of estrogen stimulation.
Pathobiology Graduate Program, Brown University, Providence, Rhode Island.
Jennifer R
JR
Wardell
Kendra M
KM
Hodgkinson
April K
AK
Binder
Kimberly A
KA
Seymour
Kenneth S
KS
Korach
Barbara C
BC
Vanderhyden
Richard N
RN
Freiman
D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics* / Q000378:metabolism; D035362:Transcription Factor TFIID / Q000235:genetics* / Q000378:metabolism
D011960:Receptors, Estrogen; D035381:TATA-Binding Protein Associated Factors; C491103:Taf4b protein, mouse; D035362:Transcription Factor TFIID; D004958:Estradiol
TAF4B; estradiol/estradiol receptor; ovarian cancer; ovary; premature ovarian failure