Progesterone receptor membrane component 1 promotes survival of human breast cancer cells and the growth of xenograft tumors

• Published in: Cancer biology & therapy 2016-03, Vol.17 (3), p.262-271
• Main Authors: Clark, Nicole C., Friel, Anne M., Pru, Cindy A., Zhang, Ling, Shioda, Toshi, Rueda, Bo R., Peluso, John J., Pru, James K.
• Format: Article
• Language: English
• Subjects: Animals; Breast cancer; Cell Growth Processes - physiology; Cell Line, Tumor; Cell Survival - physiology; endocrine; Female; Heterografts; Humans; Immunohistochemistry; Membrane Proteins - biosynthesis; Mice; Mice, Inbred NOD; Mice, Nude; Mice, SCID; PGRMC1; progesterone; Receptors, Progesterone - biosynthesis; Receptors, Progesterone - metabolism; Research Paper; TNBC; Transfection; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology; xenograft
• ISSN: 1538-4047; 1555-8576
• DOI: 10.1080/15384047.2016.1139240

Triple negative breast cancers (TNBCs) are highly aggressive and grow in response to sex steroid hormones despite lacking expression of the classical estrogen (E2) and progesterone (P4) receptors. Since P4 receptor membrane component 1 (PGRMC1) is expressed in breast cancer tumors and is known to mediate P4-induced cell survival, this study was designed to determine the expression of PGRMC1 in TNBC tumors and the involvement of PGRMC1 in regulating proliferation and survival of TNBC cells in vitro and the growth of TNBC tumors in vivo. For the latter studies, the MDA-MB-231 (MDA) cell line derived from TNBC was used. These cells express PGRMC1 but lack expression of the classical P4 receptor. A lentiviral-based shRNA approach was used to generate a stably transfected PGRMC1-deplete MDA line for comparison to the PGRMC1-intact MDA line. The present studies demonstrate that PGRMC1: 1) is expressed in TNBC cells; 2) mediates the ability of P4 to suppress TNBC cell mitosis in vitro; 3) is required for P4 to reduce the apoptotic effects of doxorubicin in vitro; and 4) facilitates TNBC tumor formation and growth in vivo. Taken together, these findings indicate that PGRMC1 plays an important role in regulating the growth and survival of TNBC cells in vitro and ultimately in the formation and development of these tumors in vivo. Thus, PGRMC1 may be a therapeutic target for TNBCs.