Characterization of human epidermal growth factor receptor and c-Src interactions in human breast tumor cells.

摘要: In C3H/10T1/2 murine fibroblasts, overexpression of both c-Src and the human epidermal growth factor (EGF) receptor 1 (HER1) is required for detection stable complexes between two molecules results in hyperactivation synergistic increases tumor formation nude mice, as compared with cells that overexpress only one pair. Elevated levels or activities HER1 also occur a subset later-stage breast cancers, suggesting interactions these could contribute to more aggressive clinical course. To determine whether cancers under same conditions fibroblasts appearance such correlates enhanced signaling through EGF increased growth, cell lines tissues were analyzed number c-Src/HER1–mediated events tumorigenicity. panel 14 lines, 10 overexpressed c-Src, these, five contained elevated exhibited an EGF-dependent association c-Src. This was present HER1/c-Src–overexpressing sample from cancer patient. Further analysis revealed phosphorylation substrate, Shc, its downstream effector, mitogen-activated protein kinase, EGF-stimulated MDA-MB-468, MDA-MB-231, BT-549 (which HER1) MCF7 ZR-75-1 c-Src). Furthermore, MDA-MB-468 MDA-MB-231 displayed tumorigenicity mice. These support hypothesis c-Src/HER1 progression certain late-stage cells. Mol. Carcinog. 21:261–272, 1998. © 1998 Wiley-Liss, Inc.