The proteins ErbB1 and ErbB2 have been found to be important indicators of poor prognosis in breast cancer. However, the mechanisms by which these molecules contribute to metastasis have not been established. In particular, determination of whether there is a rate limiting step for metastasis which is determined by these molecules is unknown. Identification of the stage of metastasis that is enhanced by ErbB1 and ErbB2 together with the molecular mechanism is critical for determining approaches for treatment and prognosis of breast cancer. He has developed new methods for evaluating tumor cells in the primary tumor, blood and target organs, and will use these methods for evaluating tumor cells in the primary tumor, blood and target organs, and will use these methods to provide important information regarding how ErbB1 and ErbB2 function in metastasis. The objective of this proposal is to determine whether chemotaxis stimulated by ErbB1 and ErbB2 is rate-limiting for metastasis. The first specific aim will be to complete development of a metastasis assay that will provide information of blood burden, cell arrest in the lungs and metastasis formation in the lungs. A pair of well-characterized rat mammary adenocarcinoma cell lines using orthotopic implantation in a syngeneic host are being used to develop the assay. The assay will then be applied to human mammary adenocarcinoma cell lines implanted in nude mice. The second specific aim will be to use this assay to evaluate the contributions of ErbB1 and ErbB2 to metastasis in terms of chemotaxis and mitogenesis. The third specific aim will evaluate the roles of the rho family of small G proteins in metastasis.
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