This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Koslowski, M. Articles by Sahin, U. Search for Related Content PubMed PubMed Citation Articles by Koslowski, M. Articles by Sahin, U.

Multiple Splice Variants of Lactate Dehydrogenase C Selectively Expressed in Human Cancer¹ ,^,2

Department of Internal Medicine, University Mainz, 55131 Mainz, Germany [M. K., Ö. T., C. B., P. K., C. H., U. S.]; Institute of Pathology, University Mainz, 55131 Mainz, Germany [H-A. L., J. B.]; Institute of Pathology, Clinical Center Bamberg, 96049 Bamberg, Germany [G. S.]; and Department of Dermatology, University Hospital Zuerich, 8091 Zuerich, Switzerland [F. O. N.]

We applied a combined data mining and experimental validation Approach for the discovery of germ cell-specific genes aberrantly expressed in cancer. Six of 21 genes with confirmed germ cell specificity were detected in tumors, indicating that ectopic activation of testis-specific genes in cancer is a frequent phenomenon. Most surprisingly one of the genes represented lactate dehydrogenase C (LDHC), the germ cell-specific member of the lactate dehydrogenase family. LDHC escapes from transcriptional repression, resulting in significant expression levels in virtually all tumor types tested. Moreover, we discovered aberrant splicing of LDHC restricted to cancer cells, resulting in four novel tumor-specific variants displaying structural alterations of the catalytic domain. Expression of LDHC in tumors is neither mediated by gene promotor demethylation, as previously described for other germ cell-specific genes activated in cancer, nor induced by hypoxia as demonstrated for enzymes of the glycolytic pathway. LDHC represents the first lactate dehydrogenase isoform with restriction to tumor cells. In contrast to other LDH isoenzymes, LDHC has a preference for lactate as a substrate. Thus LDHC activation in cancer may provide a metabolic rescue pathway in tumor cells by exploiting lactate for ATP delivery.

This article has been cited by other articles:

				M. Koslowski, U. Sahin, R. Mitnacht-Kraus, G. Seitz, C. Huber, and O. Tureci A Placenta-Specific Gene Ectopically Activated in Many Human Cancers Is Essentially Involved in Malignant Cell Processes Cancer Res., October 1, 2007; 67(19): 9528 - 9534. [Abstract] [Full Text] [PDF]

				J. Fang, Q. J. Quinones, T. L. Holman, M. J. Morowitz, Q. Wang, H. Zhao, F. Sivo, J. M. Maris, and M. L. Wahl The H+-Linked Monocarboxylate Transporter (MCT1/SLC16A1): A Potential Therapeutic Target for High-Risk Neuroblastoma Mol. Pharmacol., December 1, 2006; 70(6): 2108 - 2115. [Abstract] [Full Text] [PDF]

				M. Koslowski, U. Sahin, C. Huber, and O. Tureci The human X chromosome is enriched for germline genes expressed in premeiotic germ cells of both sexes Hum. Mol. Genet., August 1, 2006; 15(15): 2392 - 2399. [Abstract] [Full Text] [PDF]

				S. Coonrod, A. Vitale, C. Duan, S. Bristol-Gould, J. Herr, and E. Goldberg Testis-Specific Lactate Dehydrogenase (LDH-C4; Ldh3) in Murine Oocytes and Preimplantation Embryos J Androl, July 1, 2006; 27(4): 502 - 509. [Abstract] [Full Text] [PDF]

				M. L. Wahl, T. L. Moser, and S. V. Pizzo Angiostatin and Anti-angiogenic Therapy in Human Disease Recent Prog. Horm. Res., January 1, 2004; 59(1): 73 - 104. [Abstract] [Full Text]

				Q. Xu and C. Lee Discovery of novel splice forms and functional analysis of cancer-specific alternative splicing in human expressed sequences Nucleic Acids Res., October 1, 2003; 31(19): 5635 - 5643. [Abstract] [Full Text] [PDF]