Breast Cancer: Development and Characterization of an In vitro Model and an Investigation into the Capacity of Oncostatin M to Act as a Multi-Functional Tumor Promoter
Type of Culminating Activity
Master of Science in Biology
Julia Thom Oxford
Breast cancer is the leading cause of cancer deaths in women in the United States and one in nine females will acquire the disease in their lifetime. The C3(l)/SV40 Large T -antigen transgenic mouse model employs the simian virus 40 (SV 40) Large T -antigen (Tag) under control of the C3(l) regulatory sequence. The C3(l) regulatory sequence directs Tag transgene expression to the mammary gland in female mice, 100% of which develop mammary adenocarcinoma. We developed and characterized a series of C3(1)/Tag mammary carcinoma cell lines that represent progressive stages of tumor progression. The four cell lines are M28N2 and M27H4 (weakly tumorigenic), M6 (carcinoma) and M6C (metastatic). The growth rates ofthe cell lines, both in vitro and in vivo, are consistent with their representative stage of tumor progression. Additional characterization of the cell lines included analyses of cell marker expression, hormone receptor expression, and hormone-dependent growth. Next, this in vitro mouse model was used along with human breast cancer cell lines to investigate the role of the cytokine oncostatin M (OSM) in tumor progression. Previously, OSM has been shown to inhibit the growth of cancer cell lines in vitro, but our data suggests that OSM could promote tumor progression. Specifically, OSM will induce cyclooxygenase (Cox)-2 and promote the development of a metastatic phenotype in mammary carcinoma cells by stimulating Cox-z-mediated detachment of a reservoir of invasive mammary carcinoma cells from monolayer culture. In addition, OSM will induce breast cancer cells to produce vascular endothelial growth factor, the most potent pro-angiogenic factor yet identified. Collectively, these data argue that OSM could promote tumor progression in the more complex in vivo environment.
Holzer, Ryan G., "Breast Cancer: Development and Characterization of an In vitro Model and an Investigation into the Capacity of Oncostatin M to Act as a Multi-Functional Tumor Promoter" (2003). Boise State University Theses and Dissertations. 1455.