Premium
Regulation of the Na, HCO3‐cotransporter NBCn1 (SLC4A7) by a constitutively active ErbB2 receptor in MCF‐7 breast cancer cells
Author(s) -
Gorbatenko Andrej,
Olesen Christina W,
Lauritzen Gitte,
Valen Evind,
Pedersen Stine Falsig
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.882.6
Subject(s) - downregulation and upregulation , biology , mapk/erk pathway , receptor , pi3k/akt/mtor pathway , protein kinase b , signal transduction , microbiology and biotechnology , cancer research , gene , genetics
We recently showed that the Na + , HCO 3 − cotransporter NBCn1 (SLC4A7) is strongly upregulated at the mRNA and protein levels in MCF‐7 breast cancer cells upon expression of a truncated constitutively active ErbB2 receptor (ΔNErbB2) common in breast cancer. Here, we explore the mechanisms involved in this upregulation. NBCn1 expression was also increased by stimulation of full‐length ErbB receptors. NBCn1 mRNA and protein levels in ΔNErbB2‐, but not in vector‐expressing MCF‐7 cells were reduced by inhibition of ERK or Src. PI3K‐Akt inhibition reduced NBCn1 expression in both cell types, suggesting a general rather than a ΔNErbB2‐specific role of this pathway. The putative promoter region was identified bioinformatically, and reporter assays using a 1.2 kb genomic region upstream of the slc4a7 gene showed that ΔNErbB2 expression increased luciferase activity 2.5 fold, demonstrating regulation of the NBCn1 promoter by ErbB2 signaling. The possible involvement of STAT3‐ and SP1‐dependent pathways is under investigation. In conclusion, downstream from ΔNErbB2, NBCn1 expression is strongly increased, at least in part through ERK‐ and Src‐dependent pathways impacting on the NBCn1 promoter region. Funding: Novo Foundation.