EB病毒第一型潛伏膜蛋白抑制旋轉肌球素1可促進人類上皮細胞的侵襲能力

黃馪珽

doi:10.6342/NTU.2006.00603

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EB病毒第一型潛伏膜蛋白抑制旋轉肌球素1可促進人類上皮細胞的侵襲能力

Repression of TPM1 by EBV latent membrane protein 1 contributes to the invasiveness of human epithelial cells

黃馪珽 , Masters　　Advisor：陳振陽教授　　

繁體中文 DOI： 10.6342/NTU.2006.00603

旋轉肌球素；第一型潛伏膜蛋白；細胞侵襲性；肌動蛋白絲； tropomyosin ； latent membrane protein 1 ； cell invasion ； actin filament

Abstract │ Reference (102) │ Altmetrics

Abstract 〈TOP〉

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Tropomyosins are a family of actin-binding proteins that stabilize actin microfilament. High-molecular-weight (HMW) tropomyosins are encoded by TPM1 and TPM2 genes. Reduced HMW tropomyosin levels have been suggested to be associated with metastatic potential in cancer cell lines. Early studies have shown that the Epstein-Barr virus latent membrane protein 1 (LMP1) is correlated with promotion of cell invasion. TPM1 mRNA was found to be down-regulated in LMP1-expressing cell line as compared with control by cDNA microarray. In this study, we investigated whether down-regulation of TPM1-encoded HMW tropomyosin by LMP1 could promote cell invasion.
We demonstrated that TPM1 mRNA level and HMW tropomyosins were suppressed in LMP1-expressing cell lines. LMP1 could repress TPM1 gene expression through inhibition of TPM1 promoter activity. CTAR1 and CTAR2 domains were essential for repression of TPM1 promoter activity by LMP1. Forced expression of TPM1-encoded HMW tropomyosins in LMP1-expressing cells reverted LMP1-induced cell invasion. Transient expression of LMP1 in vector control cells, cell invasive ability increased approximately 2-fold. However, invasive ability was only up-regulated to 1.2-fold by LMP1 in TPM1-encoded HMW tropomyosin-expressing cells. These results suggested that LMP1 could down-regulate TPM1-encoded HMW tropomyosin, and reduction of HMW tropomyosin levels was associated with promotion of cell invasion. The mechanisms of repression of TPM1-encoded HMW tropomyosins by LMP1 and inhibition of cell invasion by HMW tropomyosins require further investigation.

Reference ( 102 ) 〈TOP〉

2. Bakin AV, Safina A, Rinehart C, Daroqui C, Darbary H and Helfman DM. (2004). A critical role of tropomyosins in TGF-beta regulation of the actin cytoskeleton and cell motility in epithelial cells. Mol Biol Cell. 15, 4682-94.
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3. Bharadwaj S and Prasad GL. (2002). Tropomyosin-1, a novel suppressor of cellular transformation is downregulated by promoter methylation in cancer cells. Cancer Lett. 183, 205-13.
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4. Bharadwaj S, Thanawala R, Bon G, Falcioni R and Prasad GL. (2005). Resensitization of breast cancer cells to anoikis by Tropomyosin-1: role of Rho kinase-dependent cytoskeleton and adhesion. Oncogene. 24, 8291-303.
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6. Blanchoin L, Pollard TD and Hitchcock-DeGregori SE. (2001). Inhibition of the Arp2/3 complex-nucleated actin polymerization and branch formation by tropomyosin. Curr Biol. 11, 1300-4.
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7. Boyd J, Risinger JI, Wiseman RW, Merrick BA, Selkirk JK and Barrett JC. (1995). Regulation of microfilament organization and anchorage-independent growth by tropomyosin 1. Proc Natl Acad Sci USA. 92, 11534-8.
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