| First Author | Missan DS | Year | 2014 |
| Journal | J Invest Dermatol | Volume | 134 |
| Issue | 9 | Pages | 2418-2427 |
| PubMed ID | 24694902 | Mgi Jnum | J:212837 |
| Mgi Id | MGI:5582338 | Doi | 10.1038/jid.2014.166 |
| Citation | Missan DS, et al. (2014) Regulation of Fibulin-2 Gene Expression by Integrin alpha3beta1 Contributes to the Invasive Phenotype of Transformed Keratinocytes. J Invest Dermatol 134(9):2418-27 |
| abstractText | The laminin-binding integrin alpha3beta1 is highly expressed in epidermal keratinocytes, where it regulates both cell-autonomous and paracrine functions that promote wound healing and skin tumorigenesis. However, the roles for alpha3beta1 in regulating gene expression programs that control the behaviors of immortalized or transformed keratinocytes remain underexplored. In the current study, we used a microarray approach to identify genes that are regulated by alpha3beta1 in immortalized keratinocytes. alpha3beta1-Responsive genes included several genes that are involved in extracellular matrix proteolysis or remodeling, including fibulin-2 and secreted protein acidic and rich in cysteine. However, alpha3beta1-dependent induction of specific target genes was influenced by the genetic lesion that triggered immortalization, as alpha3beta1-dependent fibulin-2 expression occurred in cells immortalized by either SV40 large T antigen or p53-null mutation, whereas alpha3beta1-dependent expression of secreted protein acidic and rich in cysteine occurred only in the former cells. Interestingly, quantitative PCR arrays did not reveal strong patterns of alpha3beta1-dependent gene expression in freshly isolated primary keratinocytes, suggesting that this regulation is acquired during immortalization. p53-null keratinocytes transformed with oncogenic RasV12 retained alpha3beta1-dependent fibulin-2 expression, and RNAi-mediated knockdown of fibulin-2 in these cells reduced invasion, although not their tumorigenic potential. These findings demonstrate a prominent role for alpha3beta1 in immortalized/transformed keratinocytes in regulating fibulin-2 and other genes that promote matrix remodeling and invasion. |
