Breast neoplasms are the second leading cause of cancer deaths of women in the United States. Recently, it has been shown by immunohistochemical staining of tumor biopsy tissue that nuclear localization of the odontogenic ameloblast associated protein (ODAM) correlated with staging and increased survival in patients, leading to the proposal of this protein as a novel biomarker in breast cancer. Further, ectopic expression of recombinant ODAM protein in the invasive breast carcinoma line MDA-MB-231 (231-ODAM) was shown to slow cell growth to 30-50% of that seen in control 231 cells, increase apoptosis, effect developmental change, and decrease the ability of cells to migrate or invade through extracellular matrix in transwell barrier assays. Further, this expression reduced the ability of these cells to form solid tumors by greater than 10-fold in immunodeficient mice, or establish tumor colonization of the lungs after tail vein injection. Herein, we show results of microarray and qRT-PCR data collected from 231-ODAM and control cells revealing effects of ODAM on the expression of a number of genes which have been reported to be affected by or active in the TGF-β pathway including TGF-β I-II, HAS2, Gli-2, SMADs 2, 3 and 7, PLAU and others. This suggests that ODAM interacts in part with the TGF-β pathway. When challenged with neutralizing antibodies to block TGF-β activity we observed an increase in 231-ODAM cell growth which was approximately 80% that of the 231-control line. In addition, antibody blockade of TGF-β signaling restored the ability of 231-ODAM cells to invade and migrate through matrigel-coated barriers to that of the 231-control line. Taken together, these results and others suggest that ODAM acts in part through the TGF-β pathway, which has been implicated with invasion and metastasis in breast cancer and other malignancies.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 92. doi:1538-7445.AM2012-92