INCREASED EXPRESSION OF C-MYC MESSENGER-RNA AND PROTEIN IN WALKER 256CANCER-CELLS STIMULATED BY BONE-DERIVED CONDITIONED MEDIA AND BY TRANSFORMING-GROWTH-FACTOR-BETA (TGF-BETA)

Walker 256 (W256) rat cancer cells have been reported to exhibit mitog enic responses to bone-derived factors in vitro and in vivo. We sought to determine whether this growth response is related to early oncogen e activation. After 15 and 30 min of exposure to bone-derived conditio ned medium (BDCM), there was a significant (2.5-fold) increase in c-my c (but not c-fos) mRNA levels, which returned to control (BGJb medium) levels within 1 h. The percentage of W256 cell nuclei exhibiting c-my c protein was greater after 2 h of exposure to BDCM (61.6%) compared t o controls (20.6%). BDCM is known to contain transforming growth facto r beta (TGF-beta), and in the presence of EGF (20 ng/ml), a mitogenic concentration of purified TGF-beta (0.1 ng/ml) also induced a 2.3-fold increase in c-myc mRNA expression. We conclude that the mitogenic res ponse of W256 cells to BDCM and to TGF-13 is accompanied by an early i nduction of c-myc, which may have a role in mediating the growth respo nse.