Journal article
Progesterone Receptor Membrane Component-1 Regulates the Development and Cisplatin Sensitivity of Human Ovarian Tumors in Athymic Nude Mice
Endocrinology (Philadelphia), Vol.150(11), pp.4846-4854
11/01/2009
Handle:
https://hdl.handle.net/2376/108560
PMID: 19797399
Abstract
To determine whether progesterone receptor membrane component 1 (PGRMC1) regulates the development and cisplatin (CDDP)-sensitivity of human ovarian tumors, PGRMC1 was depleted from a human ovarian cancer cell line, dsRed-SKOV-3 cells, using a short hairpin RNA knockdown 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. Compared with tumors derived from parental dsRed SKOV-3 cells, PGRMC1-deplete tumors: 1) developed in fewer mice, 2) formed less frequently, 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 respond to CDDP could be due to their poorly developed microvasculature system as judged by percentage of CD31-stained endothelial cells and/or their increased expression of ATP-binding cassette transporters, which are involved in drug resistance. Taken together, these findings indicate that PGRMC1 plays an essential role in the development and CDDP sensitivity of human ovarian tumors.
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Details
- Title
- Progesterone Receptor Membrane Component-1 Regulates the Development and Cisplatin Sensitivity of Human Ovarian Tumors in Athymic Nude Mice
- Creators
- John J Peluso - Departments of Cell Biology (J.J.P., A.G., X.L.) and University of Connecticut Health Center, Farmington, Connecticut 06030;, Departments of Obstetrics and Gynecology (J.J.P.), University of Connecticut Health Center, Farmington, Connecticut 06030Anna Gawkowska - Departments of Cell Biology (J.J.P., A.G., X.L.) and University of Connecticut Health Center, Farmington, Connecticut 06030Xiufang Liu - Departments of Cell Biology (J.J.P., A.G., X.L.) and University of Connecticut Health Center, Farmington, Connecticut 06030Toshi Shioda - Department of Tumor Biology (T.S.), Molecular Profiling Laboratory, Massachusetts General Hospital Center for Cancer Research, Harvard Medical School, Charlestown, Massachusetts 02129James K Pru - Vincent Obstetrics and Gynecology Service (J.K.P.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
- Publication Details
- Endocrinology (Philadelphia), Vol.150(11), pp.4846-4854
- Academic Unit
- Animal Sciences, Department of
- Identifiers
- 99900547114501842
- Language
- English
- Resource Type
- Journal article