Cooperation Of Rab25 Loss With Oncogenes In Breast Cancer

Breast cancer is the most common type of cancer in females worldwide. A number of genes such as BRCA1, BRCA-2, Hras, and p53 undergo mutations and contribute to tumorigenesis of the mammary tissue. The RAB guanosine triphosphates (RAS-related in brain) belong to the Ras superfamily of GTPases. The human RAS family consists of 3 proto oncogenes - H-ras, K-ras, N-ras. Rab 25 belongs to the Rab11 subfamily and plays an important role in vesicular trafficking. The Rab proteins are ubiquitously expressed. Loss of Rab 25 expression has been reported in a number of breast cancer cases and in transformed mammary cell lines containing H-ras point mutations. Human Mammary Epithelial Cells (HMEC) were obtained from healthy individuals undergoing reduction mammoplasty. The cells were immortalized by transducing with LXSN CDK4 R24C. This was followed by transduction with hTERT, catalytic subunit of the telomerase enzyme. In this study, we are trying to understand if loss of Rab25 expression in HMEC co-operates with wild and mutant H-ras as well as other oncogenes and contributes to tumorigenesis. HMEC lines in which Rab25 has been knocked down were transduced with various oncogenes, including wild type and mutant H-ras, Her-2, and IGFR1. We examined the co-operativity between loss of Rab25 and these oncogenes in migration, anchorage independent growth, stem cell marker expression, and also in vivo tumorigenesis and metastasis in nude mice. Citation Format: Krishna A. Rao, Pooja S. Joshi. Cooperation of Rab25 loss with oncogenes in breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3656.