CYTOSKELETAL PROTEINS IN ONCOGENIC TRANSFORMATION AND HUMAN NEOPLASIA

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Studies have continued on the role of tropomyosin (TM) suppression in neoplastic transformation. The mechanism of suppression of TM synthesis by retroviral oncogene expression is being explored. We have obtained evidence that TM suppression in fibroblasts transformed by retroviral oncogenes is due to the action of alpha-transforming growth factor produced as a consequence of oncogene expression. In mouse mammary epithelial cells constitutively expressing activated c-Ha-ras, Tm synthesis was not suppressed, but accumulation of newly synthesized TM was suppressed, apparently due to accumulation of actin and TM in abnormal ratios in the cytoskeleton. TM expression was also studied in a panel of established human breast cancer lines. In all but one case abnormalities in tropomyosin expression were observed in the tumor cell lines, suggesting that derangement of TM expression may be a frequent event in human neoplasia.