Sex hormone regulation of survivin gene expression.
Survivin (BIRC5) is a cell survival gene that is overexpressed in endometrial cancer and has been implicated to have a physiological role in normal endometrial function. To determine whether survivin gene expression is regulated by reproductive steroid hormones in the human endometrium, RNA was prepared from normal cycling women in the proliferative and secretory phases of the menstrual cycle. RNA was also isolated from 21 endometrial biopsies from premenopausal women at baseline and following 3 months of treatment with depot medroxyprogesterone acetate. Finally, RNA was isolated from endometrial biopsies from ten healthy postmenopausal women participating in a clinical trial of estrogen replacement therapy at baseline and following 6 months of treatment with conjugated equine estrogen. Quantitative RT-PCR analysis was used to determine survivin, insulin-like growth factor binding protein 1 (IGFBP1), Ki67, and IGF1 gene expression levels. Survivin gene expression was highest in the proliferative phase of the menstrual cycle and showed a statistically significant 4-fold increase in expression following chronic treatment with estrogens; this was strongly correlated with increased Ki67, a marker of proliferation. Survivin gene expression decreased 4.6-fold following chronic progestin treatment in the human endometrium. These data suggest that survivin transcript is regulated by estrogens and progestins in the disease-free human endometrium. The data also suggest that survivin transcript may be used as a biomarker of estrogen and progestin treatment efficacy, but validation studies must be conducted to support this conclusion.
Nabilsi
Nancy H
NH
Department of Integrative Biology and Pharmacology, University of Texas Health Science Center Houston, 6431 Fannin Street, MSB 5.132A, Houston, Texas 77030, USA.
Broaddus
Russell R
RR
McCampbell
Adrienne S
AS
Lu
Karen H
KH
Lynch
Henry T
HT
Chen
Lee-May
LM
Loose
David S
DS
D000328:Adult; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D017698:Postmenopause; D011372:Progestins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D046509:Tissue Culture Techniques
C107489:BIRC5 protein, human; D004967:Estrogens; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D011372:Progestins; D012333:RNA, Messenger; D000077022:Survivin
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