Identification of genes differentially expressed between benign and osteopontin transformed rat mammary epithelial cells

<p>Abstract</p> <p>Background</p> <p>Osteopontin is a secreted, integrin-binding and phosphorylated acidic glycoprotein which has an important role in tumor progression.</p> <p>Findings</p> <p>In this study, we have utilized suppressive subtractive hybridization (SSH) to evaluate OPN regulated gene expression, using the Rama 37 benign non-invasive rat mammary cell line and a subclone, Rama 37-OPN. Rama 37-OPN was produced by stably transfecting Rama 37 with an OPN expression vector and it demonstrates increased malignant properties <it>in vitro</it>. Sequence and expression array analysis of the respective cDNA libraries of over 1600 subtracted cDNA fragments revealed 982 ESTs, 45 novel sequences and 659 known genes. The known up-regulated genes in the Rama 37-OPN library code for proteins with a variety of functions including those involved in metabolism, cell adhesion and migration, signal transduction and in apoptosis. Four of the most differentially expressed genes between the benign and <it>in vitro </it>malignant rat mammary cell lines are tumor protein translationally controlled I (TPTI), aryl hydrocarbon receptor nuclear translocator (ARNT), ataxia telangiectasia mutated (ATM) and RAN GTPase (RAN). The largest difference (ca 10,000 fold) between the less aggressively (MCF-7, ZR-75) and more aggressively malignant (MDA MB 231, MDA MB 435S) human breast cancer cell lines is that due to RAN, the next is that due to osteopontin itself.</p> <p>Conclusion</p> <p>The results suggest that enhanced properties associated with the malignant state <it>in vitro </it>induced by osteopontin may be due to, in part, overexpression of RAN GTPase and these biological results are the subject of a subsequent publication <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>.</p