Role of the GAB2 Docking Protein in Human Breast Cancer

摘要

Deregulated receptor-tyrosine kinase (RTK) signalling is a hallmark of many breast cancers and therefore RTKs and their associated signal transducers have emerged as targets for novel therapeutic strategies as well as markers for patient prognosis. Docking proteins of the Gab/Dos family amplify RTK signals and couple these to the Ras/MAPK and Pl-3K pathways, two major signaling pathways with well established roles in tumorigenesis. Expression of the Gab2 isoform is often elevated in primary breast cancer specimens and is positively regulated by estrogen. This suggests that Gab2 plays a role in the crosstalk between steroid hormone and growth factor receptors pathways, which is implicated in the decreased estrogen sensitivity and anti-estrogen resistance of breast cancer cells. We have therefore initiated the present project to analyse the importance of Gab2 over-expression for the development and progression of breast cancer. Within the last year, we have established Gab2 overexpressing HC11 cells, a widely used model system for the analysis of signaling pathways in normal mammary epithelium. We report here the phenotypic analysis of Gab2 overexpressing HC11 cells in terms of growth factor- and serum- induced proliferation. Furthermore, we have established stable Gab2 expressing pools of the estrogen-dependent breast cancer line ZR- 75-1.