Fibronectin is distinctly downregulated in murine mammary adenocarcinoma cells with high metastatic potential

ALEJANDRO J. URTREGER; SANTIAGO E. WERBAJH; FRANK VERRECCHIA; ALAIN MAUVIEL; LYDIA I. PURICELLI; ALBERTO R. KORNBLIHTT; ELISA D. BAL DE KIER JOFFÉ

ONCOLOGY REPORTS

D.A. Spandidos

Lugar: Atenas; Año: 2006 vol. 16 p. 1403 - 1410

1021-335X

In the present work we used a murine mammary cancer model, constituted by two related adenocarcinomas with different lung metastasizing abilities, to compare their global gene expression profiles. Clontech Atlas Mouse cDNA microarrays of primary cultured tumor cells were employed in order to identify those genes that are modulated in the more metastatic variant MM3 relative to its parental tumor M3. A total of 88 from 1,176 genes were differentially expressed genes in MM3 primary cultures, being most of them (86) upregulated. Genes were grouped according to their functions as associated with signal transduction and transcription regulation (Stat1 and Zfp 92, among others), with cell adhesion and motility (cadherin 1, fibronectin), with invasion and angiogenesis (uPA, 72 kDa MMP2), with the regulation of cell proliferation and cell death (cyclins G and A2, TNF), and also included growth factors and receptors, oncogenes and tumor suppressors genes (p107, TGFb-2, TBR-I, PDGF R). Surprisingly, only 2 genes, TTF1 and fibronectin (FN), showed a significant downregulation. Notably FN expression, which loss has been associated with a malignant phenotype, was reduced about 19-fold in the more metastatic MM3 cells. Previously known differences in expression patterns associated with the metastatic capacity of MM3 and M3 adenocarcinomas, including downregulation of FN or upregulated expression of TGFb and proteases, were confirmed by the array data. The fact that FN was about the only gene significantly downregulated out of the 1,176 genes analyzed stresses the hypothesis that FN may behave as an important metastasis suppressor gene in mammary cancer.