Prolactin and Human Ovarian Cancer
Final rept. 15 Mar 2008-15 Aug 2009
CALIFORNIA UNIV RIVERSIDE
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Multiple prolactin receptors PRLRs derived from differential splicing of the same gene transcript transduce very different PRL-initiated effects on cells. In this project, we determined the kinds of PRLRs expressed by three human ovarian cancer cell lines TOV-112D, OV-90 and TOV-21G. Using quantitative PCR and Western blot, we established that the long form LF and both short forms SF1a and SF1b of the human PRLRs were expressed by all three cell lines. To clarify the functional role of these receptors, we used three different ligands for the receptor, one which in other systems promotes proliferative unmodified PRL, UPRL, one which acts as a competitive antagonist G129R, and one, a selective activator S179D. When cells were cultured in medium containing 10 FBS, UPRL had no effect on viable cell number while both of the other ligands reduced cell number. When FBS was omitted from medium, UPRL increased, while G129R and S179D decreased cell number. Further analysis showed UPRL decreased apoptosis and promoted cell migration, while S179D increased apoptosis and inhibited cell migration. The survival response and increased migration with UPRL and decrease in cell number and decreased migration in response to S179D were exaggerated by over expression of LF and SF1b.
- Medicine and Medical Research