Determining the Function of the fps/fes Proto-oncogene in Breast Development and Malignancy

摘要

The fps/fes proto-oncogene encodes a 92 kDa protein tyrosine kinase. To understand the physiological function of Fps we have generated a knockout mouse line that lacks Fps expression. Fps-knockout female mice produce litters that gain weight more slowly than wildtype mice, and develop breast tumors more quickly than wildtype mice. These data suggest that Fps participates in regulating, mammary gland development and tumorigenesis. To address these hypotheses we are examining the biological and biochemical function (s) of Fps in the mammary gland. Over the past year we have established cell culture conditions that allow for the isolation and expansion of highly purified mammary epithelial cells from wildtype and fps-null mice. These cells will be used as an in vitro model to examine the function of Fps in the mammary gland. Analysis of whole mammary tissue has revealed that Fps (and Fer) interact with protein components of the E- cadherin based adherens junction complex. Specifically, E-cadherin, beta-catenin and p120-catenin interact with Fps and Fer in the mammary gland during the lactation stage. This data is supported by confocal microscopy which demonstrates co-localization between Fps and E- cadherin. Despite the presence of fps and Fer in the adherens junction there is no detectable tyrosine phosphorylation of any of the components. Future experiments will address the precise role that Fps and Fer play in regulating the function of the adherens junction.