The product of the EMS1 gene, amplified and overexpressed in human carcinomas, is homologous to a v-src substrate and is located in cell-substratum contact sites.

Abstract

We have previously identified two genes (EMS) and PR4DI/cyclin DI) in the chromosome 11q13 region that are frequently coamplified and overexpressed in human breast cancer and in squamous cell carcinomas of the head and neck (E. Schuuring, E. Verhoeven, W. J. Mooi, and R. J. A. M. Michalides, Oncogene 7:355-361, 1992). We now report on the characterization of the 80/85-kDa protein that is encoded by the EMS) gene. Amino acid sequence comparison shows a high homology (85%) to a chicken protein that was recently identified as a substrate for the src oncogene (H. Wu, A. B. Reynolds, S. B. Kanner, R. R. Vines, and J. T. Parsons, Mol. Cell. Biol. 11:5113-5124, 1991). Immunocytochemistry reveals that in epithelial cells, the human EMS) protein is localized mainly in the cytoplasm and, to a very low extent, in protruding leading lamellae of the cell. However, in carcinoma cells that constitutively overexpress the protein as a result of amplification of the EMS) gene, the protein, except in cytoplasm, accumulates in the podosome-like adherens junctions associated with the cell-substratum contact sites. The protein was not found in intercellular adherens junctions. Our findings, and the previously reported observations in src-transformed chicken embryo fibroblasts, suggest that the EMS) protein is involved in regulating the interactions between components of adherens-type junctions. Since amplification of the 11ql3 region has been associated with an enhanced invasive potential of these tumors, overexpression and concomitant accumulation of the EMS) protein in the cell-substratum contact sites might, therefore, contribute to the invasive potential of these tumor cells.

Human cortactin as putative cancer antigen

“…No evidence of mutations in this region was found in clone MOBr-140 as compared to published cortactin gene sequence (Schuuring et al, 1993(Schuuring et al, , 1998.…”

“…This region, which apparently includes the epitope recognized by B cells, contains an SH3 domain at the C-terminus and ®ve and-a-half tandemly repeated copies of 37 amino acid residues (out of six and-a-half present in the full-size cortactin protein) that are believed to mediate binding of cortactin to ®lamentous actin in vitro. No evidence of mutations in this region was found in clone MOBr-140 as compared to published cortactin gene sequence (Schuuring et al, 1993(Schuuring et al, , 1998.…”

“…This region, which apparently includes the epitope recognized by B cells, contains an SH3 domain at the C-terminus and ®ve and-a-half tandemly repeated copies of 37 amino acid residues (out of six and-a-half present in the full-size cortactin protein) that are believed to mediate binding of cortactin to ®lamentous actin in vitro. No evidence of mutations in this region was found in clone MOBr-140 as compared to published cortactin gene sequence (Schuuring et al, 1993(Schuuring et al, , 1998.Human cortactin is a p80/p85 multidomain actin ®lament-binding protein (Schuuring et al, 1993) ®rst identi®ed as a src kinase substrate in chicken ®broblasts (Wu et al, 1991). Cortactin is involved in the signaling pathway of mitogenic receptors and adhesion molecules mediating cytoskeletal reorganization (Schuuring et al, 1993(Schuuring et al, , 1998van Damme et al, 1997;Campbell et al, 1999).…”

“…Human cortactin is a p80/p85 multidomain actin ®lament-binding protein (Schuuring et al, 1993) ®rst identi®ed as a src kinase substrate in chicken ®broblasts (Wu et al, 1991). Cortactin is involved in the signaling pathway of mitogenic receptors and adhesion molecules mediating cytoskeletal reorganization (Schuuring et al, 1993(Schuuring et al, , 1998van Damme et al, 1997;Campbell et al, 1999).…”

Signal transduction in mammary tumorigenesis: a transgenic perspective

“…Additionally, cortactin, a v-Src substrate (Wu et al, 1991), is the product of the EMS-1 locus (Schuuring et al, 1993) on human chromosome 11q13, a region frequently ampli®ed in malignant mammary carcinoma (Schuuring et al, 1992). The importance of the c-Src signaling pathway in mammary tumorigenesis has been illustrated by several important transgenic studies.…”