Endometrial cancer is the most common gynecological cancer, affecting over 600,000 women in the United States. Furthermore, increased incidence of endometrial cancer is observed among obese and premenopausal women. Currently, the standard of care is hysterectomy with the addition of radiation and chemotherapy for late stage cancers. Novel therapies are required to avoid surgical complications associated with obese patients and to preserve the fertility of young patients. MUC1 is a large, heavily glycosylated transmembrane protein that functions to lubricate mucosal surfaces, protect cells from external insult and modulates the embryo implantation process. Recent evidence suggests that the C-terminus of MUC1 is involved in intracellular signaling through interaction with several cancer-associated proteins. One of these proteins is the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that influences cellular proliferation, migration and apoptosis. Elevated MUC1 levels are associated with increased levels and signaling of EGFR in breast cancer; however, this phenomenon has not been described in the context of endometrial cancer and the mechanisms involved are not well understood in any context. To this end, human endometrial cancer cell lines were subjected to siRNA knockdown of MUC1 followed by qRT-PCR, western blotting, EGFR promoter-driven luciferase assays, proliferation and migration assays. These assays demonstrate a correlation of MUC1 levels with EGFR mRNA levels, protein levels, signaling, gene expression and cellular proliferation and migration. These results demonstrate that MUC1 control of EGFR levels and signaling also occurs in endometrial cancer-derived cell lines. Future experiments will elucidate the mechanisms by which MUC1 promotes EGFR gene expression and signaling in endometrial cancer. These insights may provide novel MUC1-based targets for endometrial cancer therapies which when used in conjunction with current non-surgical treatments may provide a therapeutic strategy that avoids surgical complications and preserves fertility. (Work supported by NIH grants RO1 HD 29963 and NCI 2P5098258-06 as well as Rice University funds to DDC).
Citation Format: Brian J. Engel, Daniel D. Carson. MUC1 increases epidermal growth factor receptor levels and signaling in endometrial cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4267. doi:10.1158/1538-7445.AM2013-4267