Abstract 4055: The transcriptional regulator TBX3 promotes progression of cells representing early premalignant breast cancer

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA The transcriptional regulator TBX3 has been shown to be elevated in metastatic breast cancer and is thought to be involved in promoting malignancy of breast and other carcinomas. In a series of cell lines derived from the same patient with breast cancer, we previously showed that metastatic 21MT-1 cells express elevated levels of TBX3, while low levels are expressed by the ductal carcinoma in situ-like 21NT cells. Here we hypothesized that upregulation of TBX3 in 21NT cells would promote their progression to a more malignant phenotype. We found that 21NT cells engineered to overexpress either isoform of TBX3 (iso1, iso2) have an altered growth in 3D Matrigel, with increased colony-forming ability, higher number of cells per colony and less spherical, more irregular colonies, consistent with increased invasiveness. Transwell assays through Matrigel showed increased invasiveness of 21NT cells overexpressing either TBX3 isoform and in vivo assay in the chick embryo similarly showed increased propensity of TBX3 over-expressing 21NT cells for extravasation. These TBX3-induced changes were associated with increased vimentin expression, but minimal change in e-cadherin expression. Overall, these results indicate that TBX3 (iso1 or iso2) expression can promote progression in a model of early breast cancer, by altering cell properties involved in cell survival/colony formation and invasiveness. Citation Format: Connor D. MacMillan, Hon S. Leong, Allen G. Clifford, Milica Krstic, Siddika Pardhan, David W. Dales, Carl O. Postenka, Ann F. Chambers, Alan B. Tuck. The transcriptional regulator TBX3 promotes progression of cells representing early premalignant breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4055. doi:10.1158/1538-7445.AM2014-4055