Abstract
The role of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) being consistently regarded as the main housekeeping gene and reference gene/protein for expression quantification in tumors has been gradually questioned and challenged by accumulated experiment evidence. The current review notified that the GAPDH expression was deregulated in lung cancer, renal cancer, breast cancer, gastric cancer, glioma, liver cancer, colorectal cancer, melanoma, prostatic cancer, pancreatic cancer and bladder cancer. Interestingly, GAPDH was commonly up-regulated in a variety of types of cancer, which was revealed to be potentially required for the cancer cell growth and tumor formation. The relevant mechanisms were also discussed in current review. This work might provide useful insights for future studies on GAPDH in tumors.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Jiang QH, Liu DG, Zheng RH et al (2002) Comparison of expression levels of S29, 18s rRNA and GAPDH genes in lung tumor tissues. Tumor 22:201–203
Rubporn A, Srisomsap C, Subhasitanont P et al (2009) Comparative proteomic analysis of lung cancer cell line and lung fibroblast cell line. Cancer Genom Proteom 6:229–237
Jung M, Ramankulov A, Roigas J et al (2007) In search of suitable reference genes for gene expression studies of human renal cell carcinoma by real-time PCR. BMC Mol Biol 8:47
Engel M, Seifert M, Theisinger B et al (1998) Glyceraldehyde-3-phosphate dehydrogenase and Nm23-H1/nucleoside diphosphate kinase A. Two old enzymes combine for the novel Nm23 protein phosphotransferase function. J Biol Chem 273:20058–20065
Revillion F, Pawlowski V, Hornez L et al (2000) Glyceraldehyde-3-phosphate dehydrogenase gene expression in human breast cancer. Eur J Cancer 36:1038–1042
Matrisian LM, Rautmann G, Magun BE et al (1985) Epidermal growth factor or serum stimulation of rat fibroblasts induces an elevation in mRNA levels for lactate dehydrogenase and other glycolytic enzymes. Nucl Acids Res 13:711–726
Valenti MT, Bertoldo F, Dalle Carbonare L et al (2006) The effect of bisphosphonates on gene expression: GAPDH as a housekeeping or a new target gene? BMC Cancer 6:49–55
Honda K, Yamada T, Hayashida Y et al (2005) Actinin-4 increases cell motility and promotes lymph node metastasis of colorectal cancer. Gastroenterology 128:51–62
Khimani AH, Mhashilkar AM, Mikulskis A et al (2005) Housekeeping genes in cancer: normalization of array data. Biotechniques 38:739–745
Kim JW, Kim TE, Kim YK et al (1999) Antisense oligodeoxynucleotide of glyceraldehyde-3-phosphate dehydrogenase gene inhibits cell proliferation and induces apoptosis in human cervical carcinoma cell lines. Antisense Nucl Acid Drug Dev 9:507–513
Sirover MA (1999) New insights into an old protein: the functional diversity of mammalian glyceraldehyde-3-phosphate dehydrogenase. Biochim Biophys Acta 1432:159–184
Tokunaga K, Nakamura Y, Sakata K et al (1987) Enhanced expression of a glyceraldehyde-3-phosphate dehydrogenase gene in human lung cancers. Cancer Res 47:5616–5619
Cuezva JM, Chen G, Alonso AM et al (2004) The bioenergetic signature of lung adenocarcinomas is a molecular marker of cancer diagnosis and prognosis. Carcinogenesis 25:1157–1163
Demarse NA, Ponnusamy S, Spicer EK et al (2009) Direct binding of glyceraldehyde-3-phosphate dehydrogenase to telomeric DNA protects telomeres against chemotherapy-induced rapid degradation. J Mol Biol 394:789–803
Vila MR, Nicolas A, Morote J et al (2000) Increased glyceraldehyde-3-phosphate dehydrogenase expression in renal cell carcinoma identified by RNA-based, arbitrarily primed polymerase chain reaction. Cancer 89:152–164
Epner DE, Partin AW, Schalken JA et al (1993) Association of glyceraldehyde-3-phosphate dehydrogenase expression with cell motility and metastatic potential of rat prostatic adenocarcinoma. Cancer Res 53:1995–1997
Alexander MC, Lomanto M, Nasrin N et al (1988) Insulin stimulates glyceraldehyde-3-phosphate dehydrogenase gene expression through cis-acting DNA sequences. Proc Natl Acad Sci USA 85:5092–5096
Blanquicett C, Johnson MR, Heslin M et al (2002) Housekeeping gene variability in normal and carcinomatous colorectal and liver tissues: applications in pharmacogenomic gene expression studies. Anal Biochem 303:209–214
Suzuki A, Iizuka A, Komiyama M et al (2010) Identification of melanoma antigens using a Serological Proteome Approach (SERPA). Cancer Genom Proteom 7:17–23
Ohl F, Jung M, Radonic A et al (2006) Identification and validation of suitable endogenous reference genes for gene expression studies of human bladder cancer. J Urol 175:1915–1920
Wang XY, Yang XY, Yang HY et al (2005) Study on the correlations of glyceraldehydes-3-phosphate dehydrogenase with human glioma. Clin J Contemp Neurol Neurosurg 5:35–39
Nguewa PA, Agorreta J, Blanco D et al (2008) Identification of importin 8 (IPO8) as the most accurate reference gene for the clinicopathological analysis of lung specimens. BMC Mol Biol 9:103
Parkin DM, Bray F, Ferlay J et al (2002) Global cancer statistics. CA Cancer J Clin 55:74–108
Schmidt B, Engel E, Carstensen T et al (2005) Quantification of free RNA in serum and bronchial lavage: a new diagnostic tool in lung cancer detection? Lung Cancer 48:145–147
Lopez-Beltran A, Scarpelli M, Montironi R et al (2006) 2004 WHO classification of the renal tumors of the adults. Eur Urol 49:798–805
Diamond I, Legg A, Schneider JA et al (1978) Glycolysis in quiescent cultures of 3T3 cells. Stimulation by serum, epidermal growth factor, and insulin in intact cells and persistence of the stimulation after cell homogenization. J Biol Chem 253:866–871
Llovet JM, Burroughs A, Bruix J (2003) Hepatocellular carcinoma. Lancet 362:1907–1917
Rubie C, Kempf K, Hans J et al (2005) Housekeeping gene variability in normal and cancerous colorectal, pancreatic, esophageal, gastric and hepatic tissues. Mol Cell Probes 19:101–109
Waxman S, Wurmbach E (2007) De-regulation of common housekeeping genes in hepatocellular carcinoma. BMC Genom 8:243–251
Gong Y, Cui L, Minuk GY (1996) Comparison of glyceraldehyde-3-phosphate dehydrogenase and 28s-ribosomal RNA gene expression in human hepatocellular carcinoma. Hepatology 23:734–737
Schek N, Hall BL, Finn OJ (1988) Increased glyceraldehyde-3-phosphate dehydrogenase gene expression in human pancreatic adenocarcinoma. Cancer Res 48:6354–6359
Chang YT, Tseng HC, Huang CC et al (2011) Relative down-regulation of apoptosis and autophagy genes in colorectal cancer. Eur J Clin Invest 41:84–92
Dydensborg AB, Herring E, Auclair J et al (2006) Normalizing genes for quantitative RT-PCR in differentiating human intestinal epithelial cells and adenocarcinomas of the colon. Am J Physiol Gastrointest Liver Physiol 290:G1067–G1074
Goidin D, Mamessier A, Staquet MJ et al (2001) Ribosomal 18S RNA prevails over glyceraldehyde-3-phosphate dehydrogenase and beta-actin genes as internal standard for quantitative comparison of mRNA levels in invasive and noninvasive human melanoma cell subpopulations. Anal Biochem 295:17–21
Ripple MO, Wilding G (1995) Alteration of glyceraldehyde-3-phosphate dehydrogenase activity and messenger RNA content by androgen in human prostate carcinoma cells. Cancer Res 55:4234–4236
Persons DA, Schek N, Hall BL et al (1989) Increased expression of glycolysis-associated genes in oncogene-transformed and growth-accelerated states. Mol Carcinog 2:88–94
Aithal HN, Toback FG, Cryst C (1980) Enhancement of renal medullary pyruvate kinase activity during cell proliferation induced by potassium depletion. Am J Physiol 238:E377–E383
Cool BL, Sirover MA (1989) Immunocytochemical localization of the base excision repair enzyme uracil DNA glycosylase in quiescent and proliferating normal human cells. Cancer Res 49:3029–3036
Mansur NR, Meyer-Siegler K, Wurzer JC et al (1993) Cell cycle regulation of the glyceraldehyde-3-phosphate dehydrogenase/uracil DNA glycosylase gene in normal human cells. Nucl Acids Res 21:993–998
Acknowledgments
This research was supported by grants from National Natural Science Foundation of China (81050010; 81171957) and Key Laboratory of Department of Education of Liaoning (LS2010050).
Conflict of interest
None.