C-ERB-2 Receptor Signalling and Breast Cancer Metastasis
Annual rept. 1 Aug 97-31 Jul 98
M D ANDERSON CANCER CENTER HOUSTON TX
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Overexpression of the c-erbB2 gene has been shown to be correlated with poor prognosis and the number of lymph node metastases in breast cancer patients. Our recent work has demonstrated that c-erbB2 indeed enhanced the intrinsic metastatic potential of human breast cancer MDA-MB-435 cells. We hypothesize that the erbB2-encoded receptor tyrosine kinase RTK may enhance metastatic potential through the RTK-signaling molecules. The purpose of this study is to test whether the increased c-erbB2 tyrosine kinase activity and tyrosine autophosphorylation on the carboxyl-terminal tail may be required for the downstream signaling involved in breast cancer metastasis. We have basically completed the Task 1, 2, and 3 of the Objective 1 as stated in the Statement of Work of our proposal. We have transfected the wild-type and mutant erbB2 genes into MDA-MB-435 cells and established a panel of wild-type and mutant erbB2 gene transfectants, which can be used as the experimental system to further our studies to understand the mechanism of erbB2 gene enhanced human breast cancer metastasis. Currently, we are comparing the metastatic potential of wild-type with erbB2 mutant transfectants that express mutated erbB2 proteins in vitro and in vivo Task 4 and 5.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research