A single nucleotide polymorphism in the human PIGK gene associates with low PIGK expression in colorectal cancer patients

Dasgupta,Santanu; Pal,Prodipto; Mukhopadhyay,Nitai  D.; Fu,Yumei; Ratovitski,Edward  A.; Moon,Chul-So; Hoque,Mohammad Obaidul; Fisher,Paul  B.; Trink,Barry

doi:10.3892/ijo.2012.1567

October 2012 Volume 41 Issue 4

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October 2012 Volume 41 Issue 4

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Article

A single nucleotide polymorphism in the human PIGK gene associates with low PIGK expression in colorectal cancer patients

Authors:
- Santanu Dasgupta
- Prodipto Pal
- Nitai D. Mukhopadhyay
- Yumei Fu
- Edward A. Ratovitski
- Chul-So Moon
- Mohammad Obaidul Hoque
- Paul B. Fisher
- Barry Trink
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Affiliations: Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA, Department of Otolaryngology, Johns Hopkins University, Baltimore, MD 21231, USA, Department of Biostatistics, Virginia Commonwealth University, Richmond, VA 23298, USA, Department of Otolaryngology, Johns Hopkins University, Baltimore, MD 21231, USA
Pages: 1405-1410
|
Published online on: July 23, 2012

https://doi.org/10.3892/ijo.2012.1567
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Abstract

Colorectal cancer (CRC) represents one of the highest incidences of cancers worldwide. Phosphatidylinositol glycan, class K (PIGK), is a crucial member of the glycosyl-phosphatidylinositol transamidase (GPIT) protein complex that attaches a diverse group of macromolecules to the plasma membrane of eukaryotes. However, the precise role of PIGK in tumorigenesis remains largely unknown. Recently, we reported low expression of PIGK protein in primary tumors compared to paired normal tissues of colorectal cancer (CRC) patients. To understand the mechanism underlying this phenomenon, we performed sequencing of all 10 exons of the PIGK gene in 45 CRC patients. Corresponding PIGK protein expression was also evaluated in these patients by immunohistochemistry. No mutation was detected in the coding regions, however, we found a single nucleotide polymorphism (C/C→C/G or G/G; rs1048575) in the 3'UTR of the PIGK gene in 67% (30/45) of the patients. Most of the patients (22/26, 85%) with the altered alleles were of Jewish origin. In comparison, 47% (8/17) of the Arabian patients exhibited the altered C/G alleles. We observed a significantly low (p<0.002) expression of PIGK protein in the patients with the altered alleles (C/G or G/G) compared to the ancestral alleles (C/C). Similarly to the CRC patients, we also examined 5 HCC patients and two HCC cell lines (Hep3B and HepG2) for PIGK genotype (SNP-1048575) and corresponding protein expression. We observed altered alleles (C/G or G/G) and corresponding low PIGK protein expression in 4 out of 5 (80%) primary HCC tumors. Among the HCC cell lines, HepG2 line exhibited ancestral C/C alleles, whereas Hep3B showed altered C/G alleles. Similar to the HCC patients, Hep3B line with the altered alleles (C/G) exhibited significantly low (Student's t-test, p<0.002) PIGK protein expression compared to the Hep3B line carrying the ancestral (C/C) alleles. To examine the exogenous PIGK protein expression status, we transiently transfected both HepG2 (C/C alleles) and Hep3B (C/G alleles) cell lines with wt-PIGK constructs. We detected exogenously expressed PIGK protein in HepG2 (C/C) cells, but no PIGK expression was detectable in Hep3B (C/G) cells at either mRNA or protein level. Our results demonstrate, for the first time, a link between the SNP 1048575 and low PIGK expression in CRC/HCC patients and also suggest a possible association between altered PIGK expression and disease susceptibility.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

A single nucleotide polymorphism in the human PIGK gene associates with low PIGK expression in colorectal cancer patients

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