Protein kinase Calpha expression confers retinoic acid sensitivity on MDA-MB-231 human breast cancer cells

Exp Cell Res. 2001 Sep 10;269(1):97-108. doi: 10.1006/excr.2001.5298.

Abstract

Retinoic acid activation of retinoic acid receptor alpha (RARalpha) induces protein kinase Calpha (PKCalpha) expression and inhibits proliferation of the hormone-dependent T-47D breast cancer cell line. Retinoic acid has no effect on proliferation or PKCalpha expression in a hormone-independent, breast cancer cell line (MDA-MB-231). To test the role of PKCalpha in retinoic acid-induced growth arrest of human breast cancer cells we established MDA-MB-231 cell lines stably expressing PKCalpha. Constitutive expression of PKCalpha did not affect proliferation of MDA-MB-231 cells but did result in partial retinoic acid sensitivity. Retinoic acid treatment of PKCalpha-MDA-MB-231 cells decreased proliferation (by approximately 40%) and inhibited serum activation of MAP kinases and induction of c-fos. Similar results were seen in MDA-MB-231 cells in which transcription of the transfected PKCalpha cDNA was reversibly induced by isopropyl beta-d-thiogalactoside. Expression of RARalpha in PKCalpha expressing MDA-MB-231 cells resulted in even greater retinoic acid responses, as measured by effects on cell proliferation, inhibition of serum signaling, and transactivation of an RARE-CAT reporter plasmid. In summary, PKCalpha synergizes with activated RARalpha to disrupt serum growth factor signaling, ultimately arresting proliferation of MDA-MB-231 cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Blood Proteins / pharmacology
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / physiopathology
  • Calcium / metabolism
  • Cell Division / drug effects
  • Cell Division / physiology*
  • Drug Interactions
  • Epidermal Growth Factor / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / physiology
  • Genes, Reporter / drug effects
  • Genes, Reporter / physiology
  • Humans
  • Isoenzymes / drug effects
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Isopropyl Thiogalactoside / pharmacology
  • Mitogen-Activated Protein Kinases / genetics
  • Protein Kinase C / drug effects
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Kinase C-alpha
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-jun / genetics
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Receptors, Retinoic Acid / drug effects
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Transfection
  • Tretinoin / metabolism
  • Tretinoin / pharmacology*
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / enzymology*

Substances

  • Antineoplastic Agents
  • Blood Proteins
  • Isoenzymes
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • Receptors, Retinoic Acid
  • Isopropyl Thiogalactoside
  • Tretinoin
  • Epidermal Growth Factor
  • PRKCA protein, human
  • Protein Kinase C
  • Protein Kinase C-alpha
  • Mitogen-Activated Protein Kinases
  • Calcium