REGULATION OF ORNITHINE DECARBOXYLASE MESSENGER-RNA LEVELS IN HUMAN BREAST-CANCER CELLS - PATTERN OF EXPRESSION AND INVOLVEMENT OF CORE ENHANCER PROMOTER ELEMENT

Ornithine decarboxylase (ODC) expression is increased by growth factor s and is obligatory for progression through the cell cycle in a wide v ariety of cell types. In this study, a variant human ODC cDNA was iden tified, sequenced, and used to probe mRNA levels in human breast tumor cell lines and xenografts. ODC mRNA was elevated about 3-fold in estr ogen receptor-negative (ER(-)) tumors (MDA-MB-231) when compared with ER-positive (ER(+)) tumors (MCF-7), as assessed by quantitative autora diographic analysis of in situ hybridization experiments. The pattern of ODC mRNA in MDA-MB-231 (ER(-)) xenografts was polarized to the extr eme periphery of the tumor, whereas the distribution of ODC mRNA was m ore evenly distributed in MCF-7 (ER(+)) xenografts. This correlates wi th hematoxylin and eosin staining patterns, suggesting that ER(+) and ER(-) xenografts have a differential dependence on:host vasculature fo r growth factor supply. ODC mRNA was elevated ii-fold in MDA-MB-231 ce lls versus MCF-7 cells when analyzed in cell culture. These relative m RNA levels correlate with increased levels of ''core'' enhancer bindin g nuclear proteins in MDA-MB-231 cells over that detected in MCF-7 cel ls.