Transcription Factor Stat5 in Invasion and Metastasis of Human Breast Cancer

摘要

The vast majority of fatal breast cancer cases involve deregulated cell proliferation and metastasis. The current project was originally funded to investigate and test the following hypothesis: Loss of activation of transcription factor State is a breast cancer progression event that favors epithelial-to- mesenchymal dedifferentiation, proliferation, invasiveness, and metastasis. However, upon completion of Pi's coursework and comprehensive exams, she changed research labs within the same Tumor Biology Ph.D. training program, but more consistent with her overall breast cancer signal transduction educational and research objectivities. The laboratory switch entailed generation of new and promising pilot data, recently presented at the 2005 Lombardi Research Fair, and a requested revised statement of work. The requested revised statement of work focuses on investigation of the role calmodulin, a universal calcium sensor protein, in cell cycle progression of breast carcinoma. Based on literature and investigations from our lab, we now hypothesize that (1) calmodulin forms a tertiary complex with p55pik and Rb, and (2) activated calmodulin, by interacting with p55pik, phosphorylates Rb and induces cell cycle progression. We have developed the necessary reagents for the study and now aim to discover the nature of interaction between p55pik and CaM, and the role CaM plays in cell cycle regulation through p55pik. These studies could lead to new therapeutic drugs against breast cancer.