Hormonal regulation of lactate dehydrogenase-A through activation of protein kinase C pathways in MCF-7 breast cancer cells

Biochemical and Biophysical Research Communications
Xiangrong LiS Safe

Abstract

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.

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Citations

Jun 5, 2014·International Journal of Cancer. Journal International Du Cancer·James L Thorne, Moray J Campbell
May 13, 2010·The International Journal of Biochemistry & Cell Biology·Katarína SmolkováPetr Ježek
May 4, 2007·The Journal of Steroid Biochemistry and Molecular Biology·Ramzi SeifeddineLiliane Massaad-Massade
Jan 18, 2006·The Journal of Steroid Biochemistry and Molecular Biology·Xiangrong LiStephen Safe
Dec 6, 2005·Journal of Theoretical Biology·Joshua DownerM D Betterton

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