Abstract 3104: HOXB7 promotes tumor progression via activation of the transformation growth factor-β signaling pathway.

Abstract

Abstract Our previous studies have shown that overexpression of Hoxb7 delays tumors onset, but promotes tumor progression and metastasis in oncogene Her2/neu-induced mammary tumorigenesis, which is reminiscent of the dual role of TGF-β in breast cancer. To investigate whether HOXB7 directly or indirectly regulates the TGF-β signaling, we examined the phosphorylation levels of SMAD3, an important mediator of TGF-beta signaling, in primary mammary tumors derived from the Hoxb7 and Her2/neu double-transgenic mice and the Her2/neu mono-transgenic mice. Phosphorylation of SMAD3 is detected in a higher percentage of primary tumor tissues from double transgenic mice than that from Her2/neu mono-transgenic mice (69.2% versus 15.4%, p < 0.05), suggesting that Hoxb7 may activate TGF-β/Smad signaling in breast tumor tissues. In line with this finding, overexpression of HOXB7 induces expression of TGF-β ligands in both mouse and human breast cancer cell lines, leading to increased cell motility and invasiveness. The acquainted phenotypes in HOXB7-overepressing cells can be reversed by pharmacologic inhibition of TGF-β signaling. Promoter deletion analysis and Chromotin-immunprocipiration assay further demonstrated that HOXB7 can directly bind to and activate the promoter of TGFβ2. More importantly, expression of HOXB7 and TGFβ2 is strongly correlated in primary breast cancer tissues and associated with advanced stages of tumor progression and reduced survival rate. Taken together, our results suggest that HOXB7 may promote tumor migration, invasion and possibly metastasis through activation of the TGF-β signaling pathway. Citation Format: Shou Liu, Hongmei Zhang, Hexin Chen. HOXB7 promotes tumor progression via activation of the transformation growth factor-β signaling pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3104. doi:10.1158/1538-7445.AM2013-3104 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.