title: Expression of c-ets-1 mRNA is associated with an invasive, EMT-derived phenotype in breast carcinoma cell lines.
abstract: We have previously observed in vitro that some stromal proteinases (MMP-2, MT1-MMP) were expressed or activated by invasive carcinoma cell lines exhibiting mesenchymal features, presumably acquired through an epithelial to mesenchymal transition (EMT). To examine the potential contribution of c-ets-1 to this phenotype, we have compared here the expression of c-ets-1 with invasiveness in vitro and expression of vimentin, E-cadherin, uPA, MMP-1 and MMP-3 in a panel of human breast cancer cell lines. Our results clearly demonstrate an association between c-ets-1 expression and the invasive, EMT-derived phenotype, which is typified by the expression of vimentin and the lack of E-cadherin. While absent from the two non-invasive, vimentin-negative cell lines, c-ets-1 was abundantly expressed in all the four vimentin-positive lines. However, we could not find a clear quantitative or qualitative relationship between the expression of c-ets-1 and the three proteinases known to be regulated by c-ets-1, except that when they were expressed, it was only in the invasive c-ets-1-positive lines. UPA mRNAs were found in three of the four vimentin-positive lines, MMP-1 in two of the four, and MMP-3 could not be detected in any of the cell lines. Intriguingly, MDA-MB-435 cells, which exhibit the highest metastatic potential of these cell lines in nude mice, expressed vimentin and c-ets-1, but lacked expression of these three proteinases, at least under the culture conditions employed. Taken together, our results show that c-ets-1 expression is associated with an invasive, EMT-derived phenotype in breast cancer cells, although it is apparently not sufficient to ensure the expression of uPA, MMP-1 or MMP-3, in the vimentin-positive cells. Such proteases regulation is undoubtedly qualified by the cellular context. This study therefore advances our understanding of the molecular regulation of invasiveness in EMT-associated carcinoma progression, and suggests that c-ets-1 may contribute to the invasive phenotype in carcinoma cells.
authors.affiliation: Department of Cell Biology and Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: C
authors.initials: C
authors.lastname: Gilles
authors.forename: M
authors.initials: M
authors.lastname: Polette
authors.forename: P
authors.initials: P
authors.lastname: Birembaut
authors.forename: N
authors.initials: N
authors.lastname: Brünner
authors.forename: E W
authors.initials: EW
authors.lastname: Thompson
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000556:secondary; D015820:Cadherins / Q000235:genetics; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology* / Q000556:secondary; D017364:Collagenases / Q000235:genetics; D004848:Epithelium / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D008648:Mesoderm / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics; D014746:Vimentin / Q000235:genetics
chemical_list: D015820:Cadherins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D014157:Transcription Factors; D014746:Vimentin; D014568:Urokinase-Type Plasminogen Activator; D017364:Collagenases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1