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Anti-oncogenic effects of tropomyosin: isoform specificity and importance of protein coding sequences
R H Braverman1, H L Cooper, H S Lee
1Laboratory of Cellular Oncology, NCI, Bethesda, Maryland 20892, USA.
Abstract:
Suppression of muscle type isoforms of tropomyosin (TM) is a common biochemical event in malignantly transformed cells. To evaluate the role of TM proteins and isoform specificity in cellular transformation, cDNAs that consist of coding sequences of TM1 (product of beta gene) and TM2 (product of alpha gene), but lacking untranslated regions (UTRs), have been expressed separately in DT (v-Ki-ras transformed NIH3T3) cells, and elevated levels of the corresponding proteins were detected. DT cells which over express TM2 manifest growth in soft agar. Elevated levels of TM1 protein in DT cells resulted in flattened cell morphology and complete abolition of anchorage independent growth. Tumorigenesis in athymic nude mice was observed in the absence of transduced TM1 mRNA. Thus, expression of TM1 protein is sufficient for tumor suppression: the UTRs of TM1 are not required for the tumor suppressive effects. Expression of TM2 protein, on the other hand, has no effect on the transformed phenotype of DT cells. These data indicate that isoforms 1 and 2 of TMs perform distinct physiological roles.
Insights
Tropomyosin (TM) isoform specificity is crucial in cancer. TM1 protein suppresses tumor growth and anchorage independence, while TM2 does not affect these transformed cell characteristics.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Muscle type tropomyosin (TM) isoforms are suppressed in malignant cells.
- TM proteins play a role in cellular transformation and tumor progression.
Purpose of the Study:
- To investigate the role of TM proteins and isoform specificity in cellular transformation.
- To determine if TM1 and TM2 expression affects the transformed phenotype of DT cells.
Main Methods:
- Expressed cDNAs of TM1 and TM2 (without untranslated regions) in v-Ki-ras transformed NIH3T3 (DT) cells.
- Detected elevated TM protein levels and assessed cellular phenotypes, including soft agar growth and tumorigenesis in nude mice.
Main Results:
- Overexpression of TM2 in DT cells led to growth in soft agar.
- Elevated TM1 protein levels resulted in flattened cell morphology and abolished anchorage-independent growth.
- TM1 protein expression was sufficient for tumor suppression, independent of UTRs, and TM2 expression had no effect on the transformed phenotype.
Conclusions:
- TM isoforms 1 and 2 perform distinct physiological roles in cellular transformation.
- TM1 protein exhibits tumor suppressive effects, while TM2 does not influence the transformed phenotype.
- Isoform specificity of tropomyosin is critical for regulating cellular transformation and tumor suppression.