Role of erbB-2 and erbB-3 in the Activation of Phosphatidylinositol 3-Kinase

摘要

We sought to assess the importance of cooperative interaction between p185erbB-2 and erbB-3 in the growth factor-independent proliferation and neoplastic transformation of breast carcinoma cells with c-erbB-2 gene amplification. We have now successfully produced cell populations derived from MCF-10A normal mammary epithelial cells that overexpress c-erbB-2 at very high levels comparable to that seen in breast carcinoma+ cells with c-erbB-2 gene amplification. While the original clones of MCF-10AerbB-2 cells overexpress c- erbB-2 at only moderate levels and are not tumorigenic in nude mice, MCF- 19AerbB-2shH cells selected for high-level c-erbB-2 overexpression with growth factor,independence in culture show a high level of constitutive PI 3-kinase activity and a highly transformed phenotype both in culture and in vivo. In addition, key observations were made during the course of these studies which provide important information concerning the survival and growth of cells, in the absence of growth factors that occurs as a function of the level of c-erbB-2 gene overexpression.