Protein kinase Calpha regulates Ets1 transcriptional activity in invasive breast cancer cells.

Ralph K. Lindemann, Melanie Braig, Pia Ballschmieter, Theresa A. Guise, Alfred Nordheim, Jürgen Dittmer

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

We have previously shown that PKC inhibitors interfere with the Ets1/Smad3-dependent regulation of parathyroid hormone-related protein (PTHrP) P3 promoter activity by TGFbeta in invasive MDA-MB-231 breast cancer cells. By examining PKC expression in a variety of breast cancer cell lines, the protein level of PKCalpha was found to be much higher in Ets1-expressing MDA-MB-231 and MDA-MB-435 breast cancer cells than in Ets1-deficient MCF-7 and SK-BR3 cells. No correlation of Ets1 expression with the expression of other PKC subtypes (PKCbeta1, PKCbeta2, PKCdelta or PKCepsilon) could be observed. In contrast to MDA-MB-231 cells, PKCalpha-deficient MCF-7 cells do not support Ets1-induced activation of the PTHrP P3 promoter suggesting that PKCalpha may be important for Ets1 activity. A constitutively active form of PKCalpha was found to potentiate the P3 promoter activation by Ets1 alone and in synergy with Smad3. PKCalpha, but not PKCepsilon, also induced phosphorylation of the Ets1 protein. Both PKCalpha effects on Ets1 depended on the exon VII domain of Ets1. Using verapamil and ionomycin, we could show that PKCalpha induces Ets1 phosphorylation independent of calcium mobilization. Collectively, our data suggest that PKCalpha may regulate Ets1 activity in invasive breast cancer cells.

Original languageEnglish (US)
Pages (from-to)799-805
Number of pages7
JournalInternational journal of oncology
Volume22
Issue number4
StatePublished - Apr 2003
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Protein kinase Calpha regulates Ets1 transcriptional activity in invasive breast cancer cells.'. Together they form a unique fingerprint.

  • Cite this

    Lindemann, R. K., Braig, M., Ballschmieter, P., Guise, T. A., Nordheim, A., & Dittmer, J. (2003). Protein kinase Calpha regulates Ets1 transcriptional activity in invasive breast cancer cells. International journal of oncology, 22(4), 799-805.