This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.A funded project (CA114094-01: Analysis of AND-34 in human breast cancer) seeks to establish why over-expression of a specific protein, AND-34, allows normally estrogen-dependent human breast cancer cell lines to become resistant to growth inhibition by anti-estrogens. AND-34 is expressed in murine B cells and plays a role in lymphoid adherence and migration. We have shown that AND-34 binds to a focal adhesion adapter protein, p130Cas. Over-expression of AND-34, but not two other closely related family members (NSP-1 and NSP-2) leads to activation of the cyclin D1 promoter and anti-estrogen resistance. All three family members bind to p130Cas. There is some evidence that over-expression of AND-34 may affect phosphorylation of p130Cas. This does not appear to occur by a Src family kinase-dependent mechanism, although p130Cas is a well known Src family kinase substrate. We are using mass spectrometry to establish where p130Cas is phosphorylated following over-expression of AND-34. We will compare the phosphorylation pattern of p130Cas from this AND-34 over-expressing cell line with that observed in MCF-7 cells.
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