Progesterone receptor membrane component-1 (PGRMC1) is the mediator of progesterone’s antiapoptotic action in spontaneously immortalized granulosa cells as revealed by PGRMC1 small interfering ribonucleic acid treatment and functional analysis of PGRMC1 m

To determine whether progesterone receptor membrane component 1 (PGRMC1) regulates the de-velopment and cisplatin (CDDP)-sensitivity of human ovarian tumors, PGRMC1 was depleted from a humanovarian cancer cell line, dsRed-SKOV-3 cells, using a short hairpin RNAknockdown approach. Compared with parental dsRed-SKOV-3 cells, the PGRMC1-deplete cells grew slower in vitro and did not show progesterone’s (P4) antiapoptotic effect. In fact, P4 induced apoptosis in PGRMC1-deplete cells in a dose-dependent manner. When transplanted into the peritoneum of athymic nude mice, parental dsRed-SKOV-3 cells developed numerous tumors, which were classified as either typical or oxyphilic clear cell tumors. CDDP increased the percentage of apoptotic nuclei in typical clear cell tumors and P4 attenuated CDDP-induced apoptosis. In contrast, the percentage of apoptotic nuclei in oxyphilic clear cell tumors was low (1%) and was not significantly affected by CDDP and/or P4. Comparedwith tumors derived fromparental dsRed SKOV-3 cells, PGRMC1-deplete tumors: 1) developed in fewer mice, 2) formed less fre-quently, 3) appeared smaller, and 4) resulted in fewer oxyphilic clear cell tumors. These PGRMC1-deplete tumors were not responsive to CDDP’s apoptotic effects. The failure to re-spond to CDDP could be due to their poorly developed microvasculature system as judged b