A serologically identified tumor antigen encoded by a homeobox gene promotes growth of ovarian epithelial cells

Ovarian carcinomas are thought to arise from cells of the ovarian surface e pithelium by mechanisms that are poorly understood, Molecules associated wi th neoplasia are potentially immunogenic, but few ovarian tumor antigens ha ve been identified, Because ovarian carcinomas can elicit humoral responses in patients, we searched for novel tumor antigens by immunoscreening a cDN A expression library with ovarian cancer patient serum. Seven clones corres ponding to the homeobox gene HOXB7 were isolated, ELISAs using purified rec ombinant HOXB7 protein revealed significant serologic reactivity to HOXB7 i n 13 of 39 ovarian cancer patients and in only one of 29 healthy women (P < 0.0001). Ovarian carcinomas were found to express HOXB7 at markedly higher levels than normal ovarian surface epithelium, suggesting that immunogenic ity of HOXB7 in patients could be associated with its elevated expression i n ovarian carcinomas, Overexpression of HOXB7 in immortalized normal ovaria n surface epithelial cells dramatically enhanced cellular proliferation, Fu rthermore, HOXB7 overexpression increased intracellular accumulation and se cretion of basic fibroblast growth factor, a potent angiogenic and mitogeni c factor, These results reveal HOXB7 as a tumor antigen whose up-regulated expression could play a significant role in promoting growth and developmen t of ovarian carcinomas.