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Altered expression of multiple genes involved in retinoic acid biosynthesis in human colorectal cancer

Ekaterina S Kropotova1, Olga L Zinovieva, Alisa F Zyryanova

  • 1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russian Federation.

Pathology Oncology Research : POR
|March 7, 2014
PubMed

Insights

Reduced production of all-trans-retinoic acid (atRA) in colorectal cancer is linked to decreased expression of key synthesizing enzymes, potentially impacting cell growth and differentiation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • All-trans-retinoic acid (atRA), derived from vitamin A, is crucial for regulating cell proliferation and differentiation.
  • Reduced atRA biosynthesis is implicated in various human tumors, including colorectal cancer.
  • Specific atRA-synthesizing enzymes involved in colorectal tumors remain largely undetermined.

Purpose of the Study:

  • To investigate the expression patterns of genes responsible for atRA biosynthesis in normal colorectal tissues, primary carcinomas, and cancer cell lines.
  • To identify specific enzymes whose expression is altered in colorectal cancer.
  • To understand the implications of these alterations on atRA production and colorectal cancer progression.

Main Methods:

  • Gene expression analysis using RT-PCR.
  • Identification of relevant genes through transcriptomic data analysis (ESTs, RNA-seq, microarrays).
  • Comparison of gene expression in normal tissues, primary tumors, and cancer cell lines.

Main Results:

  • Significant downregulation of ADH1B, ADH1C, RDHL, RDH5, and AKR1B10 mRNA levels in most colorectal carcinomas.
  • Reduced expression of RALDH1 and increased expression of CYP26A1 observed.
  • Similar expression patterns found in human colon cancer cell lines.
  • Decreased expression of ADH1B and ADH1C correlates with colorectal cancer progression from adenoma to advanced stages.

Conclusions:

  • Colorectal cancer exhibits dysregulation across the atRA biosynthesis pathway.
  • Reduced expression of key retinol-oxidizing enzymes (ADH1B, ADH1C) likely impairs atRA production.
  • Diminished atRA biosynthesis may contribute to altered cell growth and differentiation, promoting colorectal cancer progression.

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