title: Aberrant survivin expression in endometrial hyperplasia: another mechanism of progestin resistance.
abstract: Up to 30% of failure rate in endometrial hyperplasia patients treated by progestin urges more detailed understanding of the mechanisms involved in progestin resistance. Survivin is a key regulator in the antiapoptotic network, and overexpression of survivin has been reported in endometrial hyperplasia and cancer. This study investigated the role of survivin in progestin resistance in endometrial hyperplasia. Pre- and post-treatment endometrial hyperplasia tissue samples from 23 women were examined for changes in survivin expression related to the administration of progestins. The impact of continuous or intermittent progestin treatment on survivin expression in Ishikawa cells was examined by the western blot. Survivin immunoreactivity was present in epithelial compartment of all pre-progestin-treated endometrial hyperplasia samples with mean nuclear indices 78 and cytoplasmic indices 114. In the 15 progestin responders, an average of 19.5-fold decrease of survivin expression was seen in epithelial nuclei (P<0.001) and 8-fold decrease in epithelial cytoplasm (P<0.001). In the eight non-responders, no significant changes in survivin expression were detected. With in vitro Ishikawa cells, survivin expression was effectively inhibited by either 72-h continuous treatment with 10 muM medroxyprogesterone acetate or 72 h after medroxyprogesterone acetate withdrawal. Our results indicated that dysregulation of survivin expression in hyperplastic endometrium may be part of the molecular mechanisms for progestin resistance. Intermittent, rather than continuous, progestin treatment may be more effective clinically for the treatment of endometrial hyperplasia.
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital, Shanghai Medical College Fudan University, Shanghai, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Chen
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Youji
authors.initials: Y
authors.lastname: Feng
authors.forename: Oluwole
authors.initials: O
authors.lastname: Fadare
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Ai
authors.forename: Hongyan
authors.initials: H
authors.lastname: Jin
authors.forename: Chao
authors.initials: C
authors.lastname: Gu
authors.forename: Wenxin
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D004351:Drug Resistance / Q000235:genetics*; D004714:Endometrial Hyperplasia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D008875:Middle Aged; D011372:Progestins / Q000008:administration & dosage*; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D015415:Biomarkers; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D011372:Progestins; D000077022:Survivin