Evaluation of c-KIT in ovarian surface epithelial cells and ovarian tumours

Abstract

Ovulation is a putative risk factor for ovarian cancer, and may be attributed to proliferating ovarian surface epithelial (OSE) cells interacting with the extracellular matrix (ECM) during ovulatory wound repair. We investigated the effects of ECM and cellular density on OSE cell morphology, proliferation, and expression of c-Kit, a proto-oncogene expressed in 70% of ovarian tumours. Fibrillar collagen I caused significant changes in morphology and proliferation but monomeric ECM had no effect. Normal human ovaries co-expressed KIT, collagen I and fibronectin in 75% of abnormal OSE structures. At increased cellular densities, rat OSE cells expressed increased levels of Kit. Retrovirus-mediated expression of c-Kit in OSE caused a significant increase in proliferation. Additionally, sequence analysis of c-KIT in 21 ovarian tumours revealed no mutations. These results suggest a relationship between KIT and collagen I in OSE and that cellular density in the OSE regulates KIT, which increases cell proliferation and may contribute to transformation.