NDLI: Altered Expression of Multiple Genes Involved in Retinoic Acid Biosynthesis in Human Colorectal Cancer

Content Provider	Springer Nature Link
Author	Kropotova, Ekaterina S. Zivieva, Olga L. Zyryava, Alisa F. Dybovaya, Vera I. Prasolov, Vladimir S. Beresten, Sergey F. Oparina, Nina Yu. Mashkova, Tamara D.
Copyright Year	2014
Abstract	All-trans-retinoic acid (atRA), the oxidized form of vitamin A (retinol), regulates a wide variety of biological processes, such as cell proliferation and differentiation. Multiple alcohol, retinol and retinaldehyde dehydrogenases (ADHs, RDHs, RALDHs) as well as aldo-keto reductases (AKRs) catalyze atRA production. The reduced atRA biosynthesis has been observed in several human tumors, including colorectal cancer. However, subsets of atRA-synthesizing enzymes have not been determined in colorectal tumors. We investigated the expression patterns of genes involved in atRA biosynthesis in normal human colorectal tissues, primary carcinomas and cancer cell lines by RT-PCR. These genes were identified using transcriptomic data analysis (expressed sequence tags, RNA-sequencing, microarrays). Our results indicate that each step of the atRA biosynthesis pathway is dysregulated in colorectal cancer. Frequent and significant decreases in the mRNA levels of the ADH1B, ADH1C, RDHL, RDH5 and AKR1B10 genes were observed in a majority of colorectal carcinomas. The expression levels of the RALDH1 gene were reduced, and the expression levels of the cytochrome CYP26A1 gene increased. The human colon cancer cell lines showed a similar pattern of changes in the mRNA levels of these genes. A dramatic reduction in the expression of genes encoding the predominant retinol-oxidizing enzymes could impair atRA production. The most abundant of these genes, ADH1B and ADH1C, display decreased expression during progression from adenoma to early and more advanced stage of colorectal carcinomas. The diminished atRA biosynthesis may lead to alteration of cell growth and differentiation in the colon and rectum, thus contributing to the progression of colorectal cancer.
Starting Page	707
Ending Page	717
Page Count	11
File Format	PDF
ISSN	12194956
Journal	Pathology & Oncology Research
Volume Number	20
Issue Number	3
e-ISSN	15322807
Language	English
Publisher	Springer Netherlands
Publisher Date	2014-03-06
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Colorectal cancer Retinoic acid biosynthesis Gene expression Tumor progression Cancer Research Oncology Pathology Immunology Biomedicine general
Content Type	Text
Resource Type	Article
Subject	Cancer Research Pathology and Forensic Medicine Oncology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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