Prolactin inhibits apoptosis of ovarian carcinoma cells induced by serum starvation or cisplatin treatment.
Prolactin, a peptide hormone essential for the development and function of reproductive organs, is involved in development of breast, prostate and colorectal cancers. However, the role of prolactin on the carcinogenesis of ovarian carcinomas is unclear. In this study, we show that mRNA of prolactin receptor is expressed in 5 out of 9 ovarian carcinoma cell lines, 15 out of 17 cases of surgical samples and all of normal ovarian surface epithelium, while prolactin transcript is detected only in 1 ovarian carcinoma cell line and in 1 of the surgical samples. For the prolactin receptor-positive ovarian carcinoma cells, exogenous prolactin did not affect the proliferation but markedly inhibited apoptosis. Therefore, actual cell growth was enhanced by prolactin in a dose-dependent manner. The blocking of prolactin receptor by antibody severely impaired the antiapoptotic and growth-promoting effects of prolactin. Interestingly, the cisplatin-induced cell death of the prolactin receptor-positive cells was significantly inhibited by pretreatment with prolactin. These findings indicate a responsiveness of ovarian carcinomas to prolactin and suggest that the prolactin/prolactin receptor system may be a new therapeutic target of ovarian carcinomas.
Asai-Sato
Mikiko
M
Department of Obstetrics, Gynecology and Molecular Reproductive Science, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Nagashima
Yoji
Y
Miyagi
Etsuko
E
Sato
Ken
K
Ohta
Ichiro
I
Vonderhaar
Barbara K
BK
Hirahara
Fumiki
F
D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D016895:Culture Media, Serum-Free; D017931:DNA Primers; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000601:surgery; D011388:Prolactin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D011981:Receptors, Prolactin / Q000235:genetics*; D014407:Tumor Cells, Cultured
D016895:Culture Media, Serum-Free; D017931:DNA Primers; D012333:RNA, Messenger; D011981:Receptors, Prolactin; D011388:Prolactin; D002945:Cisplatin