Regulation of CD44s by the c-sis oncogene product was investigated. Both CD44s protein and mRNA were comparably upregulated, consistent with some degree of transcriptional regulation; its ligand binding was also activated in confluent but not in sparse cultures of sis-transformed Balb/c 3T3 cells. CD44s was also elevated in confluent cultures of parental 3T3 cells treated with conditioned media from confluent c-sis transformants (but not from 3T3 cells); these media (but not media from ras transformants or parental 3T3 cells) contained platelet-derived growth factor (PDGF)-immunoreactive material. CD44s upregulation by these media could be partially blocked by anti-PDGF antibodies. These media also induced activation via tyrosine autophosphorylation and activation-dependent downregulation of PDGF beta-receptors. sis-transformed 3T3 cells contained low levels of PDGF receptor, but CD44 levels could still be increased in these cells by addition of PDGF. These results suggest that CD44s is upregulated in confluent cultures of c-sis-transformed cells by autocrine growth factors, including PDGF, secreted into the cell's microenvironment.

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