Decreased expression of high molecular weight Tropomyosins in Squamous Cell Carcinoma of Esophagus (SCCE)
Session type: Poster / e-Poster / Silent Theatre session
Tromyosins are a family of cytoskeletal proteins that binds to and stabilize actin in microfilaments. Non-muscle cells express multiple isoforms of tropomyosins that include three high molecular weight isoforms: TM1,TM2 and TM3. Although the role of tropomyosins in muscle contraction is well established, their role in non-muscle cells is less clear. The expression of major isoforms of TM (high molecular weight ) is downregulated in cells that are transformed by oncogenes, which is likely involved in the morphological alterations, loss of density inhibition, and anchorage independent growth which are typical phenotypes for transformed cell. Moreover, expression of specific TM isoforms is suppressed in some human carcinoma, such as breast, bladder, prostate and brain.
In this study the expression of high molecular weight tropomyosins were analyzed in tumor tissues of SCCE relative to their adjacent normal tissues, and also in human esophagus carcinoma cell line, TE15. Quantitation of TM isoforms were examined both at the level of protein and mRNA, applying western blot analysis and real time RT-PCR, respectively.
In carcinoma of esophagus all three high molecular weight TM isoforms were significantly reduced at the level of protein expression relative to their normal samples. Furthermore, TM1, TM2, and TM3 were rather undetectable in TE15 cell line. Real Time RT-PCR analysis revealed that in tumor samples both TPM1 and TPM2 genes were suppressed at the level of transcription. The expression level of TPM1 and TPM2 mRNA were found to be less than 1% of that observed in normal samples.
Collectively, these results suggest that the expression of high molecular weight tropomyosin isoforms are significantly reduced in SCCE, both at the level of translation and transcription, therefore, down regulation of TM isoforms, as a member of actin cytoskeleton, could play an important role in tumorogenesis of SCCE.