Abstract
Abstract Background: Recent clinical evidence suggest that expression of BCL2 and its antagonist BAD are good prognosticators for survival in breast cancer patients. BAD protein was previously shown by us to inhibit cyclin D1 expression and cJun activation, both may enhance invasiveness of tumor cells(Fernando et al JBC 07). However, the role of BAD and other BCL2 family proteins in invasion/metastasis of breast cancer is poorly characterized. Methods: By immunohistochemistry nuclear and cytoplasmic staining of several proteins including BAD in normal epithelial was compared to that of cancer cells in human specimens. Western blotting and ELISA methods were used to compare BAD overexpressing MCF7 breast cancer cells with control cells for the expression of variety of signaling molecules, proteins that take part in metastasis and invasion and ability of cells to invade was measured. PCR was used to measure m RNA levels and reporter constructs utilized for transcriptional factor activity studies. Results: Grade II breast cancer specimens express less total and phosphorylated forms of BAD in nuclei and cytoplasm compared to normals. BAD expression decreased Sp1, β-catenin and STAT proteins, which may increase cyclin D1 in vitro. BAD inhibited activation of the CRE and AP1 elements, and phosphorylation of BAD on S112 and S136 is required for this activity. BAD inhibited the Ras/MEK/ERK pathway and JNK, which may underlie inactivation of c Jun. BAD, like BCL2, may decrease metastasis,therefore, ability of BAD to modulate the expression of metastasis related proteins were measured and MMP10, VEGF, SNAIL, CXCR4, E-cadherin, and ***TlMP2 were regulated by BAD with a concomitant reduction in cell invasion. Conclusion: Higher expression of BAD in breast cancer and a role in metastasis and proliferation suggests that BAD is valuable prognostic marker in breast cancer and a multi functional protein. Further given the overwhelming clinical evidence that BCL2 prolongs survival, a reevaluation of the role of BCL2 family proteins in metastasis is urgently required. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-02-11.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
