Expression of Endogenous Suppressors of HER2 Overexpression in Breast Cancer

摘要

The purpose of this project is to identify and confirm negative regulator proteins that suppress ErbB2 expression in normal breast epithelial cells, but permit ErbB2 overexpression when dysregulated by tumor cells. The strategy is to use a very sensitive quantitative PCR method to assess transcript levels of candidate modulator genes in normal and tumor tissue from patient samples and mouse models. In the first year of this three year project, PCR primers were designed and initially characterized in terms of their abilities to specifically amplify target genes. In addition, screens of candidate ErbB2 negative regulator genes were initiated using human and mouse tissue samples. The preliminary data from FvB transgenic mice that overexpress ErbB2 in the mammary gland indicate that several genes are consistently upregulated or downregulated during the normal-to-tumor transition. These observations indicate that our overall strategy is likely to ultimately identify dysregulated ErbB modulators in human tumors, the focus of year two of the project.