? Ovarian carcinoma is the fifth most common cause of cancer among women in the USA, with more than 23,000 new cases diagnosed and approximately 14,000 deaths each year. In Mexico, ovarian cancer is the seventh cause of cancer among women. In our hospital, ovarian cancer corresponds to 15% of all the cancers with an average of 100 cases per year. The epithelial ovarian carcinomas, which make up more than 90% of human ovarian cancers, arise in the ovarian surface epithelium. The etiology and early events in the progression of these carcinomas are among the least understood of all major human malignancies, but the majority of evidence suggests that reproductive factors and genetics may play roles in the origin of this disease. ? Recent studies have demonstrated that a new family of growth factors [epithelin, granulins and acrogranin (the precursor)] have regulatory activities on preimplantation mouse embryo, normal epithelial and tumoral cells in rodents and human, following interesting signal transduction pathways and are over expressed in some kind of human cerebral tumors, renal cell epithelial carcinomas. The objectives of this proposal are determined if acrogranin is expressed in early stages in the embryo and if it has some role in ovarian development in the mouse. In the second aim we want to examine if acrogranin is over expressed in other kinds of epithelial tumors (ovary) and if it is over expression is associated with malignancy. In the third aim will be explored the signal transduction pathway in epithelial ovary cancer cell lines, we consider that acrogranin activate the MAP kinases pathway for stimulate DNA synthesis, and it does not follow the ras pathway in epithelial ovary cancer. ? The results of the proposed experiments will lead to significant advances in understanding the participation of acrogranin in the pathogenesis and or malignant progression of the cancer at the clinical and molecular levels. A rational design of selective reagents that target the acrogranin pathway should afford new therapeutics targets for human cancer where acrogranin has a role. ? ? ?
| Cuevas-Antonio, R; Cancino, C; Arechavaleta-Velasco, F et al. (2010) Expression of progranulin (Acrogranin/PCDGF/Granulin-Epithelin Precursor) in benign and malignant ovarian tumors and activation of MAPK signaling in ovarian cancer cell line. Cancer Invest 28:452-8 |
