Gene expression and methylation status of 14-3-3sigma in human renal carcinoma tissues

Shufang Liang1, Yuhuan Xu, Guobo Shen

  • 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.

IUBMB Life
|June 13, 2008
PubMed

Insights

14-3-3sigma gene expression is frequently lost in kidney tissues due to DNA hypermethylation. This epigenetic silencing increases with cancer progression, impacting normal, para-cancerous, and renal carcinoma tissues.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • 14-3-3sigma (also known as stratifin) is a tumor suppressor gene.
  • Loss of 14-3-3sigma expression via methylation is implicated in various cancers.
  • Its methylation status in human renal carcinoma remains understudied.

Purpose of the Study:

  • To investigate the expression and methylation status of 14-3-3sigma in human renal tissues.
  • To determine the correlation between 14-3-3sigma gene silencing and its DNA methylation.
  • To assess methylation patterns across normal, para-cancerous, and cancerous kidney tissues.

Main Methods:

  • Reverse Transcription Polymerase Chain Reaction (RT-PCR) for gene expression analysis.
  • Immunohistochemistry for protein expression assessment.
  • Methylation-Specific PCR (MSP) to evaluate DNA methylation status.
  • In vitro demethylation using 5-aza-2'-deoxycytidine in OS-RC-2 cells.

Main Results:

  • 14-3-3sigma expression was lost in 27 out of 31 renal tissues examined.
  • Hypermethylation of 14-3-3sigma was observed in 14/16 renal carcinoma tissues.
  • Methylation was also prevalent in para-cancerous and normal kidney tissues, increasing with malignancy.
  • Demethylation treatment in OS-RC-2 cells partially restored 14-3-3sigma mRNA expression.

Conclusions:

  • 14-3-3sigma gene silencing is strongly associated with DNA hypermethylation in renal tissues.
  • The frequency and extent of 14-3-3sigma methylation increase with the progression of kidney malignancy.
  • Epigenetic silencing of 14-3-3sigma is a common event in renal carcinogenesis and even in normal kidney tissue.