Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/262
Title: Regulation of Lactate Dehydrogenase Genes in Endocrine Resistant Human Breast Cancer Cells
Authors: Reem Salem Al-Shammari 
Supervisor: Prof. Yunus Luqmani
Keywords: Lactate Dehydrogenase Genes Endocrine Resistant Human Breast Cancer Cells
Issue Date: 2016
Publisher:  Kuwait university - college of graduate studies
Abstract: Cancer cells differ from normal cells in their preference for ATP generation from glucose conversion to lactate by lactate dehydrogenase (LDH), instead of the more efficient process of oxidative phosphorylation. This is presumably an adaptive response to the hypoxic tumour environment prior to neovascularisation but seems to persist even under normoxia, offering potential for therapeutic intervention with inhibitors targeting glycolytic enzymes. In this study we examined expression of LDH-A and LDH-B and their five isoforms in a series of cancerous and non-cancerous human cell lines using Taqman-RT-PCR, immunoblotting and isozyme profiling using an "in-gel" enzyme assay. Intra-and-extracellular lactate concentrations and LDH-activity were determined by biochemical assay. LDH-A was expressed at variable levels in all cell lines whilst LDH-B was only detected in the estrogen receptor (ER)–ve lines. Restoration of LDH-B expression in ER+ve cells was achieved by treatment with 5'-azacytidine and trichostatin A suggesting epigenetic control of its transcription related to ER expression. All LDH isozymes were expressed in all ER-ve lines (mainly isoforms 2,3,4). Predominantly LDH4 and 5 isoforms were expressed in ER+ve cells. High extracellular LDH-activity was observed in ER-ve (pII) compared to ER+ve cell lines (MCF7 and Sh2.1). Variable lactate concentrations were noted in the intra-and-extracellular fractions of the various cell lines, but with significantly higher amounts in the extracellular fraction of pII compared with MCF7 and Sh2.1 cell lines. Further experiments are needed to clarify the complex relationship between the two LDH genes, their isoforms and catalytic activity in terms of lactate production under normoxic and hypoxic conditions and how this is affected by ER, and how this may relate to invasive capacity.
URI: http://hdl.handle.net/123456789/262
Appears in Programs:2050 Molecular Biology

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