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The PTEN regulator DJ-1 is associated with hTERT expression in clear cell renal cell carcinoma

Raviprakash T Sitaram1, Claire J Cairney, Pawel Grabowski

  • 1Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.

International Journal of Cancer
|April 23, 2009
PubMed

Insights

DJ-1 regulates tumor suppressor PTEN and impacts PI3K-AKT/PKB signaling, affecting c-Myc and human telomerase reverse transcriptase (hTERT). This pathway is significant in clear cell renal cell carcinoma (ccRCC) but not linked to prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • DJ-1 is identified as a regulator of the tumor suppressor PTEN.
  • DJ-1 influences PI3K-AKT/PKB signaling, potentially affecting c-Myc.
  • Human telomerase reverse transcriptase (hTERT) can be activated by c-Myc and AKT/PKB.

Purpose of the Study:

  • To investigate the signaling pathway involving DJ-1, c-Myc, and hTERT in renal cell carcinoma (RCC).
  • To analyze the functional significance of this pathway in different RCC subtypes and cell lines.

Main Methods:

  • Analysis of DJ-1, c-Myc, and hTERT mRNA expression in 176 RCC samples and kidney cortex tissue.
  • Experimental validation using cell lines with siRNA knockdown of DJ-1.
  • Assessment of hTERT promoter activity following DJ-1 transfection and c-Myc binding site mutation.

Main Results:

  • DJ-1 mRNA expression was significantly higher in clear cell RCC (ccRCC) and papillary RCC (pRCC) compared to kidney cortex.
  • Elevated c-Myc and hTERT RNA levels were observed in ccRCC and pRCC.
  • DJ-1 positively correlated with c-Myc and hTERT in ccRCC, with DJ-1 knockdown reducing c-Myc and hTERT expression.
  • DJ-1 transfection upregulated hTERT promoter activity, dependent on c-Myc binding sites.

Conclusions:

  • The study supports a functional link between DJ-1, c-Myc, and hTERT in ccRCC.
  • This pathway's functional significance is demonstrated experimentally, though not associated with proliferation, telomere length, or prognosis in ccRCC.

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