Inhibition of Breast Cancer Metastasis by Heregulin-Beta 1

The major goal of this Idea proposal is to determine whether and how HRG-Beta1 inhibits breast cancer metastasis and to identify the functional domains that are sufficient for inhibition of breast cancer metastasis. We have fulfilled most of the proposed tasks for the first year of the grant support. We demonstrated that the recombinant HRG-Beta1 can transcriptionally upregulate gelatinases activity. We found that HRG-Beta1 induces the aggregation a metastasis associated property of breast cancer cells via activation of PI-3-K but independent of ERK Cancer Res. 591620-1625, 1999. To determine the effect of HRG- f3 1 in metastasis in vivo, we subcloned the extracellular domain of the full length HRG-Beta1 into the pSecTag2 expression vector, transfected it into MDA-MB-435 and MCF-7 cell, and established stable transfectants. To further delineate the domains of HRG-Beta1 that regulates invasionmetastasis of breast cancer cells, we have also cloned the egf-like domain of HRG-Beta1 to pSecTag2 expression vector. We are transfecting the egf-like domain of HRG-Beta1 into MDA-MB-435 and MCF-7 cells to establish stable transfectants. These initial works have paved a productive avenue for the next grant-support year, when we will gain more insights regarding the role of HRG-Betal in breast cancer metastasis.