Hormonal regulation of lactate dehydrogenase-A through activation of protein kinase C pathways in MCF-7 breast cancer cells.
Lactate dehydrogenase A (LDH-A) is hormonally regulated in rodents, and increased expression of LDH-A is observed during mammary gland tumorigenesis. The mechanisms of hormonal regulation of LDH-A were investigated using a series of deletion and mutant constructs derived from the rat LDH-A gene promoter. Results of these studies show that constructs containing the -92 to -37 region of the LDH-A promoter are important for basal and E2-induced transactivation, and mutation of the consensus CRE motif within this region results in significant loss of basal activity and hormone-responsiveness. Gel mobility shift assays using nuclear extracts from MCF-7 cells show that both CREB and ATF-1 interact with the CRE. Studies with kinase inhibitors show that E2-induced activation of this CRE is dependent on protein kinase C, and these data indicate that LDH-A is induced through a non-genomic pathway of estrogen action.
Li
Xiangrong
X
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
Qin
Chunhua
C
Burghardt
Robert
R
Safe
Stephen
S
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D004958:Estradiol / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000235:genetics; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000235:genetics
D017362:Cyclic AMP Response Element-Binding Protein; D007527:Isoenzymes; D011994:Recombinant Proteins; D004958:Estradiol; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D011493:Protein Kinase C