Multiple Splice Variants of Lactate Dehydrogenase C Selectively Expressed in Human Cancer , Export

@article{citeulike:2526331, abstract = {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.}, author = {Koslowski, Michael and Tureci, Ozlem and Bell, Carolin and Krause, Patricia and Lehr, Hans-Anton and Brunner, Joachim and Seitz, Gerhard and Nestle, Frank O. and Huber, Christoph and Sahin, Ugur}, citeulike-article-id = {2526331}, citeulike-linkout-0 = {http://cancerres.aacrjournals.org/cgi/content/abstract/62/22/6750}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/12438276}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=12438276}, day = {15}, journal = {Cancer Res}, keywords = {biomarkers, cancer, lactate, ldh\_isoform, warburg}, month = {November}, number = {22}, pages = {6750--6755}, posted-at = {2008-03-13 13:56:38}, priority = {2}, title = {Multiple Splice Variants of Lactate Dehydrogenase C Selectively Expressed in Human Cancer ,}, url = {http://cancerres.aacrjournals.org/cgi/content/abstract/62/22/6750}, volume = {62}, year = {2002} }

TY - JOUR ID - citeulike:2526331 L3 - citeulike-article-id:2526331 N2 - 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. IS - 22 JF - Cancer Res EP - 6755 TI - Multiple Splice Variants of Lactate Dehydrogenase C Selectively Expressed in Human Cancer , VL - 62 SP - 6750 KW - biomarkers KW - cancer KW - lactate KW - ldh_isoform KW - warburg AU - Koslowski, Michael AU - Tureci, Ozlem AU - Bell, Carolin AU - Krause, Patricia AU - Lehr, Hans-Anton AU - Brunner, Joachim AU - Seitz, Gerhard AU - Nestle, Frank AU - Huber, Christoph AU - Sahin, Ugur PY - 2002/11/15/ UR - http://cancerres.aacrjournals.org/cgi/content/abstract/62/22/6750 ER -