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

We have previously identified two genes (EMS1 and PRAD1/cyclin D1) in the chromosome 11q13 region that are frequently coamplified and overex pressed 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 character ization of the 80/85-kDa protein that is encoded by the EMS] gene. Ami no acid sequence comparison shows a high homology (85%) to a chicken p rotein that was recently identified as a substrate for the src oncogen e (H. Wu, A. B. Reynolds, S. B. Kanner, R. R. Vines, and J. T. Parsons , Mol. Cell. Biol. 11:5113-5124, 1991). Immunocytochemistry reveals th at in epithelial cells, the human EMS1 protein is localized mainly in the cytoplasm and, to a very low extent, in protruding leading lamella e of the cell. However, in carcinoma cells that constitutively overexp ress the protein as a result of amplification of the EMS1 gene, the pr otein, except in cytoplasm, accumulates in the podosome-like adherens junctions associated with the cell-substratum contact sites. The prote in was not found in intercellular adherens junctions. Our findings, an d the previously reported observations in src-transformed chicken embr yo fibroblasts, suggest that the EMS1 protein is involved in regulatin g the interactions between components of adherens-type junctions. Sinc e amplification of the 11q13 region has been associated with an enhanc ed invasive potential of these tumors, overexpression and concomitant accumulation of the EMS1 protein in the cell-substratum contact sites might, therefore, contribute to the invasive potential of these tumor cells.