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

Xiangrong Li, Chunhua Qin, Robert Burghardt, Stephen Safe

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)625-634
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume320
Issue number3
DOIs
StatePublished - Jul 30 2004

Keywords

  • Estrogen
  • Lactate dehydrogenase A
  • Non-genomic
  • PKC activation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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