Relative Contribution of Ornithine Decarboxylase (ODC) Versus S- adenosylmethionine Decarboxylase (SAMDC) to Human Breast Cancer Progression and Development

摘要

Although polyamines (PA) play an important role in breast cancer phenotype, the relative contribution of the two PA biosynthetic enzymes, ornithine decarboxylase (ODC) and S- adenosylmethionine decarboxylase (SAMDC) is not known. Our data show that overexpression of SAMDC in MCP-7 breast cancer cells leads to a more benign biologic behavior characterized by decreased invasiveness in vitro and reduced tumorigenicity in nude mice. These effects may be mediated by the compensatory downregulation of ODC leading to reduced cellular putrescine and spermidine contents. In contrast, in experiments conducted in MDA-MB-435 and MDA-MB-231 breast cancer cells, we have observed that ODC adversely affects breast cancer phenotype and, most importantly, contributes to the development of distant metastasis. In the aggregate, our data point to ODC as an attractive target in the adjuvant therapy of breast cancer.