Hepatitis B X-interacting protein (HBXIP) is a novel oncoprotein. In this study, we found that the expression levels of HBXIP were positively associated with those of S-phase kinase-associated protein 2 (Skp2) in clinical breast cancer tissues and cell lines. Moreover, we found that HBXIP was able to stimulate the promoter of Skp2 through binding to the -640/-443 region in Skp2 promoter involving activating E2F transcription factor 1 (E2F1). Skp2 plays crucial roles in HBXIP-enhanced proliferation of breast cancer cells in vitro and in vivo. We conclude that HBXIP up-regulates Skp2 via activating E2F1 to promote proliferation of breast cancer cells.
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