INTERACTION BETWEEN THE ADHESION RECEPTOR, CD44, AND THE ONCOGENE PRODUCT, P185(HER2), PROMOTES HUMAN OVARIAN TUMOR-CELL ACTIVATION

In this study we have examined the interaction between CD44s (the stan dard form) and the p185(HER2) proto-oncogene in the ovarian carcinoma cell line. Surface biotinylation followed by wheat germ agglutinin col umn chromatography and anti-CD44-mediated immunoprecipitation indicate that both CD44s and p185(HER2) are expressed on the cell surface and most importantly, that these two molecules are physically linked to ea ch other via interchain disulfide bonds, We have also determined that hyaluronic acid stimulates CD44s-associated p185(HER2) tyrosine kinase activity, leading to an increase in the ovarian carcinoma cell growth , After transfection of the ovarian carcinoma cell line with the adeno virus 5 EIA gene, which is known to repress p185(HER2) expression, we observed that both surface CD44s expression and CD44s-mediated cell ad hesion to hyaluronic acid are significantly reduced in the transfectan t cells compared with the control cells. These data suggest that down- regulation of p185(HER2) blocks CD44s expression and subsequent adhesi on function, Our findings also indicate that the CD44s-p185(HER2) inte raction is both functionally coupled and biosynthetically regulated, W e believe that direct ''cross-talk'' between these two surface molecul es (i.e, CD44s and the p185(HER2)) may be one of the most important si gnaling events in human ovarian carcinoma development.