Immune Netw.  2004 Dec;4(4):237-243. 10.4110/in.2004.4.4.237.

Gene Expression Changes Associated with Sustained p16 Expression in Hepatocellular Carcinoma Cells

• Oh SJ
• Im JY
• Jung CH
• Lee YB

• KMID: 1515491
• DOI: http://doi.org/10.4110/in.2004.4.4.237

Abstract

BACKGROUND
The normal functions of the cell cycle inhibitor p16INK4a are frequently inactivated in many human cancers. Over 80% of hepatocellular carcinoma (HCC) cases lack a functional p16/Rb pathway. p16/Rb pathway, as well as p53 pathway, is considered as one of key components of tumor suppression. METHODS: To study the roles of p16INK4a in HCC, a stable cell line expressing exogenous p16 was generated from SNU-449 hepatocellular carcinoma cells lacking endogenous p16, and suppression subtractive hybridization (SSH) was performed in parallel with the control cells. RESULTS: 1) SSH identifies fibronectin (FN1), crystallin alphaB (CRYAB), Rac1, WASP, RhoGEF, and CCT3 as differentially-expressed genes. 2) Among the selected genes, the up- regulation of FN1 and CRYAB was confirmed by Northern blot, RT-PCR and by proteomic methods. CONCLUSION: These genes are likely to be associated with the induction of stress fiber and stabilization of cytoskeleton. Further studies are required to clarify the possible role of p16 in the signal transduction pathway.

Keyword

Suppression subtractive hybridization; sustained p16 expression; hepatocellular carcinoma; differential gene expression

MeSH Terms

Blotting, Northern
Carcinoma, Hepatocellular*
Cell Cycle
Cell Line
Crystallins
Cytoskeleton
Fibronectins
Gene Expression*
Humans
Rho Guanine Nucleotide Exchange Factors
Signal Transduction
Stress Fibers
Wasps
Crystallins
Fibronectins