Study of glyceraldehyde-3-phosphate dehydrogenase expression in the tumor process of: Breast, cervix and prostate cancers

Bouchra Elkhalfi, Nezha Senhaji, Hakima Benomar, Abdelaziz Soukri

Laboratoire d’Anatomo-Cyto-Pathologie, Institut Pasteur du Maroc, Casablanca, Morrocco.
Laboratoire de Physiologie et Génétique Moléculaire, Département de Biologie, Faculté des Sciences, Université Hassan II, Casablanca, Morrocco.

DOI: 10.4236/abc.2012.24041                

Abstract

W Tumor proliferation of cancer cells requires a high intake of oxygen by angiogenesis. Deep cancer cells suffer from asphyxia and meet their energy needs through the enzymes of glycolysis. The anti-angio- genesis approach has been recognized for therapeutic purposes, but the deep cancers, difficult to reach by this therapy, could be targeted by inhibiting an enzyme of the glycolytic cycle. Our work focused on the study of the expression of GAPDH, a key enzyme of glycolysis, in cervix, breast and prostate tumors, for two approaches: Fundamental and targeted therapeutics. 60 samples, taken at the Anatomopathology laboratory of the Pasteur Institute of Morocco, were examined histologically and immunohistochemically, demonstrating the expression and cellular localization of GAPDH. The three organs have shown an overex-pression of GAPDH in tumor tissues. At the cellular level, the localization of GAPDH in cancer tissue is diffuse but mostly nuclear whereas it remains focused at the membrane and/or the cytoplasm in benign tumor tissues. From these results we could assume that GAPDH is involved in the cancer process and draws attention to a possible new nuclear role that could be either specific to one form or different isoforms of GAPDH enzyme.

Keywords

Cancer; GAPDH; Immunohistochemistry; Expression; Isoforms

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Sygusch, J., Azema, L. and Dax, C. (2006) A first weapon against cancer metastases. Univalor Journal, 1, 1-2.
[2]	Warburg, O.H. (1956) On the origin of cancer cells. Science, 123, 309-314. doi:10.1126/science.123.3191.309
[3]	Soukri, A., Valverde, F., Hafid, N., Elkebbaj, M.S. and Serrano, A. (1996) Occurrence of a differential expression of the glyceraldehyde-3-phosphate dehydrogenase gene in muscle and liver from euthermic and induced hibernating jerboa (Jaculus orientalis). Gene Journal, 181, 139-145. doi:10.1016/S0378-1119(96)00494-5
[4]	Iddar, A., Valverde, F., Serrano, A. and Soukri, A. (2002) Expression, purification and characterization of recombinant non-phosphorylating NADP-dependent glyceralde- hyde-3-phosphate dehydrogenase from Clostridium acetobutylicum. Journal of Protein Expression and Purification, 25, 519-526. doi:10.1016/S1046-5928(02)00032-3
[5]	Fothergill-Gilmore, L.A. and Pam, M. (1993) Evolution of Glycolysis. Journal of Progress in Biophysics and Molecular Biology, 95, 105-135. doi:10.1016/0079-6107(93)90001-Z
[6]	Figge, R.M., Schubert, M., Brinkman, H. and Cerff, R. (1999) Glyceraldehyde phosphate dehydrogenase gene diversity in eubacteria an eukaryotes: Evidence for intra- and inter-kingdom gene transfer. Journal of Molecular Biology and Evolution, 16, 429-440. doi:10.1093/oxfordjournals.molbev.a026125
[7]	Habenicht, A. (1997) The non-phosphorylating glycerol- dehyde-3-phosphate dehydrogenase: Biochemistry, structure, occurrence and evolution. Journal of Biological Chemistry, 378, 1413-1419.
[8]	Bruns, G.A.P. and Gerald, P.S. (1976) Human glycerol- dehyde-3-phosphate dehydrogenase in man-rodent so- matic cell hybrids. Science, 192, 54-56. doi:10.1126/science.176725
[9]	Sirover, M.A. (1999) New insights into an old protein: The functional diversity of mammalian glyceraldehyde- 3-phosphate dehydrogenase. Journal of Biochimica and Biophysica Acta, 1432, 159-184. doi:10.1016/S0167-4838(99)00119-3
[10]	Barbini, L., Rodríguez, J., Dominguez, F. and Vega, F. (2007) Glyceraldehyde-3-phosphate dehydrogenase exerts different biologic activities in apoptotic and prolifer- ating hepatocytes according to its subcellular localization. Journal of Molecular and Cellular Biochemistry, 300, 19- 28. doi:10.1007/s11010-006-9341-1
[11]	Sirover, M.A. (2005) New nuclear functions of the gly- colytic protein, glyceraldehyde-3-phosphate dehydrogenase, in mammalian cells. Journal of Cellular Bio- chemistry, 95, 45-52. doi:10.1002/jcb.20399
[12]	Pitot, H.C. (1986) The biochemistry of neoplasia in vivo. Fundamentals of Oncology, Marcel Dekker, New York, 323-346.
[13]	Zhou, Y.Y.X, Stoffer, B.J., Bonafe. N., Gilmore-Hebert, M., McAlpine, M. and Chambers, S.K. (2008) The multifunctional protein glyceraldehyde-3-phosphate dehy- drogenase is both regulated and controls colony-stimulating factor-1 messenger RNA Stability in Ovarian Can- cer. Journal of Molecular Cancer Research, 6, 1375- 1384. doi:10.1158/1541-7786.MCR-07-2170
[14]	Du, Z.-X., Wang, H.Q., Zhang, H.Y. and Gao, D.X. (2007) Involvement of glyceraldehyde-3-phosphate de- hydrogenase in tumor necrosis factor-related apoptosis- inducing ligand-mediated death of thyroid cancer cells. Journal of endocrinology, 148, 4352. doi:10.1210/en.2006-1511
[15]	Laffargue, F., Dargent, D. and Piana, L. (2002) Contribution des Sociétés fran?aises de chirurgie d’organe. Bulletin du Cancer, 89, 52-54
[16]	Parkin, D.M., Bray, F.I. and Devesa, S.S. (2001) Cancer burden in the year 2000 the global picture. Journal of European journal of Cancer, 3, 4-66.
[17]	Mountassif, D., Baibai, T., Fourrat, F., Moutaouakkil, A., Iddar, A., El Kebbaj, M.S. and Soukri, A. (2009) Immunoaffinity purification and characterization of Glyceral- dehyde-3-phosphate dehydrogenase from human eryth- rocytes. Journal of Acta Biochimica & Biophysica Sinica, 41, 309-406.
[18]	Pederson, P.L. (1978). Tumor mitochondria and the bio-energetics of cancer cells. Journal of Progress in Experimental Tumor Research, 22, 198-274.
[19]	Epner, D.E., Partin, A.W., Schalken, J.A., Isaacs, J.T. and Coffey, D.S. (1993) Association of glyceraldehyde-3- phosphate dehydrogenase expression with cell motility and metastatic potential of rat prostatic adenocarcinoma. Journal of Cancer Research, 53, 1995-7.
[20]	Kim, J.W., Kim, S.J., Han, S.M., Paik, S.Y., Hur, S.Y., Kim, Y.W., Lee, J.M. and Namkoong, S.E. (1998) Increased glyceraldehyde-3-phosphate dehydrogenase gene expression in human cervical cancers. Journal of Gynecologic Oncology, 71, 266-269. doi:10.1006/gyno.1998.5195
[21]	Correa, C.R., Bertollo, C.M., Zouain, C.S. and Goes A.M. (2010) Glyceraldehyde-3-phosphate dehydrogenase as an associated antigen on human breast cancer cell lines MACL-1 and MGSO-3. Journal of Oncology Reports, 24, 677-685.
[22]	Kim, J.W., Kim, T.E., Kim, Y.K., Kim, Y.W., Kim, S.J., Lee, J.M., Kim, I.K. and Namkoong, S.E. (1999) Antisense oligodeoxynucleotide of glyceraldehyde-3-phos- phate dehydrogenase gene inhibits cell proliferation and induces apoptosis in human cervical carcinoma cell lines. Journal of Antisense & Nucleic Acid Drug Development, 9, 507-513. doi:10.1089/oli.1.1999.9.507
[23]	Shan, L., Xiang, G., Hoestje, S. and Epner, D.E. (2002) Identification of an additional hypoxia responsive element in the glyceraldehyde-3-phosphate dehydrogenase gene promoter. Journal of Biochimica and Biophysica Acta (BBA)—Gene Structure and Expression, 1574, 2152-2156.
[24]	Sirover, M.A. (1990) Cell cycle regulation of DNA repair enzymes and pathways. In: Milo, G.E. and Casto, B.C., Eds., Transformation of Human Diploid Fibroblasts, CRC Press, Boca Raton, 29-55.