Suppression of tropomyosin synthesis, a common biochemical feature of oncogenesis by structurally diverse retroviral oncogenes.

Abstract

To identify proteins whose production may be altered as a common event in the expression of structurally diverse oncogenes, we compared two-dimensional electropherograms of newly synthesized proteins from NIH/3T3 cell lines transformed by a variety of retroviral oncogenes, from cellular revertant lines, and from a line (433.3) which expresses the v-ras oncogene in response to corticosteroids. Most alterations in the synthesis of specific proteins detected by this approach appeared to be the result of selection during prolonged cultivation and were probably unrelated to the transformation process. However, we detected seven proteins whose synthesis was strongly suppressed in cell lines transformed by each of the six retroviral oncogenes we studied and whose production was fully or partially restored in two cellular revertant lines. Suppression of two of these proteins was also correlated with the initial appearance of morphological alteration during corticosteroid-induced oncogene expression in 433.3 cells. These proteins (p37/4.78 and p41/4.75) were identified as tropomyosins, a group of at least five cytoskeletal proteins. Transformation by the papovaviruses simian virus 40 and polyomavirus caused no suppression of synthesis of these tropomyosins. This indicates that suppression of tropomyosin synthesis is not a nonspecific response by cells to being forced to grow with the transformed phenotype but is specifically associated with oncogenesis by diverse retroviral oncogenes. The results are consistent with the hypothesis that the different biochemical processes initiated by expression of structurally diverse retroviral oncogenes may converge on a limited number of common targets, one of which is the mechanism which regulates the synthesis of tropomyosins.

Suppression of src-induced transformed phenotype by expression of tropomyosin-1

“…Changes in the expression of a number of micro®lament-associated proteins during neoplastic transformation have been well documented (Button et al, 1995;Jammey and Chaponnier, 1995). For example, the expression of gelsolin (Vandekerckhove et al, 1990), vinculin (Ferna ndez et al, 1992), a-actinin (GluÈ ck et al, 1993) and tropomyosins (Leonardi et al, 1982;Cooper et al, 1985;Lin et al, 1985;Matsumura et al, 1983), which bind to and/or modulate the polymerization status of actin, is reported to be down regulated as the cells acquire malignant phenotype.…”

“…For example, in ®broblasts, a total of ®ve di erent TMs are expressed: TM1 (M r , 41 kDa), TM2 (M r , 36 kDa) and TM3 (M r , 35 kDa), each with 284 aa, are referred to as high M r isoforms. TM4 and TM5 (each with M r of 32 kDa) contain 247 aa and are described as low M r isoforms (Cooper et al, 1985;Prasad et al, 1993). The function of TMs in muscle cells, in conjunction with the troponins, as the components of actin-myosin contractile apparatus, is well-de®ned (Lin et al, 1997;Pittenger et al, 1994).…”

“…The goal of our research is to understand the role of TMs in cell physiology and to elucidate the involvement of TMs in neoplastic transformation of cells (Cooper et al, 1985(Cooper et al, , 1987Bhattacharya et al, 1988Bhattacharya et al, , 1990. Our previous work has established that TM1 suppression is a common biochemical change in the cells undergoing neoplastic transformation, by various oncogenic modalities (Cooper et al, 1985).…”

“…Our previous work has established that TM1 suppression is a common biochemical change in the cells undergoing neoplastic transformation, by various oncogenic modalities (Cooper et al, 1985). For example, in murine ®broblasts transformed with v-kiras (DT cells) the expression of TM1 is suppressed to 50% levels found in normal NIH3T3 cells.…”

“…The v-src-transformed NIH3T3 cells (3T3/src cells) express a reduced level (50%) of TM1 protein and its cognate mRNA compared to NIH3T3 cells (Cooper et al, 1985). The 3T3/src cells readily form colonies in agar, in anchorage independent fashion, as well as manifest morphological features concomitant with the transformed phenotype.…”