Desmocollin 3 mediates follicle stimulating hormone-induced ovarian epithelial cancer cell proliferation by activating the EGFR/Akt signaling pathway.
Follicle-stimulating hormone (FSH) is associated with the pathogenesis of ovarian cancer. We sought to explore whether desmocollin 3 (Dsc3) mediates FSH-induced ovarian epithelial cancer cell proliferation and whether the EGFR/Akt signaling pathway may be involved in this process. Dsc3 positivity in ovarian tissue specimens from 72 patients was assessed by immunohistochemistry. The positive expression rates of Dsc3 were similar in ovarian cancer tissues (24/31:77.4%) and borderline ovarian tumor tissues (18/22:81.8%) (P>0.05), but were significantly higher in these cancerous tissues than in benign ovarian cyst tissues (3/19:15.8%) (P<0.05). Consistently, the expression of Dsc3 in four out of five ovarian cancer cells (HO8910, Skov3ip, Skov and Hey cells, but not ES-2 and in borderline ovarian MCV152 tumor cells was higher than in the immortalized ovarian epithelial cell line, Moody. FSH up-regulated the expression of Dsc3 and EGFR in a dose- and time-dependent manner. Furthermore, a converse relationship between the expression of Dsc3, EFGR and PI3K/Akt signaling was elucidated using RNA interference and PI3K/Akt inhibitor in the absence and presence of FSH. A role for these proteins in FSH-induced cell proliferation was verified, highlighting their interdependence in mediating ovarian cancer cell function. These results suggest that Dsc3 can mediate FSH-induced ovarian cancer cell proliferation by activating the EGFR/Akt signaling pathway.
Department of Gynecology and Obstetrics, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.
Xiao
X
Yang
Department of Gynecology and Obstetrics, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.
Jing
J
Wang
Department of Gynecology and Obstetrics, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.
Wen-Ping
WP
Li
Department of Gynecology and Obstetrics, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.
Zhi-Jun
ZJ
Jin
Department of Gynecology and Obstetrics, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.
Xiao-Jun
XJ
Liu
D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D051187:Desmocollins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
C490356:DSC3 protein, human; D051187:Desmocollins; D047428:Protein Kinase Inhibitors; D005640:Follicle Stimulating Hormone; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt
Dsc3; EGFR/Akt signaling pathway; Ovarian cancer; cell proliferation; follicle-stimulating hormone (FSH)