Transcription Factor Stat5 in Invasion and Metatasis of Human Breast Cancer

摘要

Class IA PI3Ks are regarded the most important in regulating cell proliferation and tumorigenesis. The p55 protein is a regulatory subunit of class IA PI3K. In vitro study has demonstrated that the NH2-terminal of p55 is sufficient to bind the cell cycle regulatory protein pRb. Association between calmodulin and p55 in 293T cells has been demonstrated by calmodulin sepharose beads pull-down assay in the previous report. We also demonstrated that p55 stabilized the interaction between calmodulin and Rb. We aim to uncover the cell cycle and growth regulation effect of p55 protein by overexpression and RNA interference analysis. Here we confirmed the co-immunoprecipitation of Rb with p55 protein. However, by overexpression of full-length p55 in MCF-7 cells or knocking down of p55 in AU565 cells, we could not demonstrate a significant effect on the cell cycle or cell growth. Using SK-Br-3 cells as a model for breast cancer cells, we found a shift in composition among the PI3K regulatory subunits once p55 was manipulated. Other PI3K regulatory subunits such as p85 and p50 increased when p55 was knocked down, and p85 decreased when p55 was overexpressed. This could account for the marginal effect we observed when we expressed or down-regulated p55 in breast cancer model systems.