Scaffold Attachment Factor SAFB1: A New Player in G2/M Checkpoint Control

摘要

Loss of G2/M checkpoint plays an important role in tumorigenesis, however, few genes involved in this checkpoint control have been shown to be deregulated in human breast tumors. SAFB1 is a multifunctional protein which maps to a locus of high LOH, and mutations have been identified inboth breast cancer cell lines and tumors. Our preliminary data show that inactivation of SAFB1 in MEFs result in loss of G2/M checkpoint control, and that loss of SAFB1 expression is associated with Taxotere resistance in human breast tumors. We therefore hypothesize that SAFB1 is critical for G2/M checkpoint control, and that its inactivation results in resistance to breast cancer therapies that utilize a block in G2/M and subsequent apoptosis. We will identify the mechanism by which SAFB1 controls the G2/M checkpoint, and will subsequently analyze whether Taxotere-resistant tumors show altered expression of genes involved in these pathway(s).