FSH stimulates ovarian cancer cell growth by action on growth factor variant receptor

• Published in: Molecular and cellular endocrinology Vol. 267; no. 1; pp. 26 - 37
• Main Authors: Li, Y., Ganta, S., Cheng, C., Craig, R., Ganta, R.R., Freeman, L.C.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 15.03.2007
• Subjects: Alternative Splicing - drug effects; Amino Acid Sequence; Animals; Base Sequence; Cell Line, Transformed; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclic AMP - metabolism; Enzyme Activation - drug effects; Exons - genetics; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Follicle Stimulating Hormone - pharmacology; Follicle stimulating hormone receptor; Humans; Mice; Molecular Sequence Data; Mutant Proteins - metabolism; Ovarian cancer; Ovarian Neoplasms - pathology; Ovarian surface epithelium; Receptors, FSH - chemistry; Receptors, FSH - genetics; Receptors, FSH - metabolism; Signal Transduction - drug effects; Swine; Transcription, Genetic - drug effects; Follicle stimulating hormone receptor; Ovarian surface epithelium; Ovarian cancer
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2006.11.010

A number of FSH receptor (FSH-R) isoforms with distinct structural motifs and signaling paradigms have been described, including a single transmembrane domain variant that functions as a growth factor type receptor (FSH-R3). This study tested the hypothesis that FSH can stimulate ovarian cancer cell proliferation by acting on FSH-R3, using the tumorigenic mouse ovarian surface epithelial cell (MOSEC) line ID8. FSH enhanced ID8 proliferation in a concentration-dependent fashion. Moreover, FSH-treatment of ID8 elicited intracellular events consistent with activation of FSH-R3 and distinct from those associated with activation of the canonical G-protein coupled FSH-R isoform (FSH-R1). Specifically, the FSH-R3 signaling pathway included cAMP-independent activation of ERK downstream of an SNX-482 sensitive component likely to be the Cav2.3 calcium channel. Northern analysis using probes specific for exons 7 and 11 of FSH-R identified consistently only one 1.9 kb transcript. Immunoblot analysis confirmed expression of FSH-R3 but not FSHR-1 in ID8. Together, these data suggest that FSH-R3 signaling promotes proliferation of ovarian cancer cells.