Eag1 and bestrophin 1 are up-regulated in fast-growing colonic cancer cells

Melanie Spitzner, Joana Raquel Martins, René Barro Soria, Jiraporn Ousingsawat, Kerstin Scheidt, Rainer Schreiber, Karl Kunzelmann

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Ion channels like voltage-gated ether-á-go-go (Eag1) K+ channels or Ca2+-activated Cl- channels have been shown to support cell proliferation. Bestrophin 1 (Best1) has been proposed to form Ca2+-activated Cl- channels in epithelial cells. Here we show that original T84 colonic carcinoma cells grow slowly (T 84-slow) and express low amounts of Eag1 and Best1, whereas spontaneously transformed T84 cells grow fast (T84-fast) and express high levels of both proteins. Both Eag1 and Best1 currents are up-regulated in T84-fast cells. Eag1 currents were cell cycle-dependent with up-regulation during G1/S transition. T 84-slow, but not T84-fast, cells formed tight monolayers when grown on permeable supports. RNA interference inhibition of Eag1 and Best1 reduced proliferation of T84-fast cells, whereas overexpression of Best1 turned T84-slow into fast-growing cells. Eag1 and Best1 improve intracellular Ca2+ signaling and cell volume regulation. These results establish a novel role for bestrophins in cell proliferation.

Original languageEnglish (US)
Pages (from-to)7421-7428
Number of pages8
JournalJournal of Biological Chemistry
Volume283
Issue number12
DOIs
StatePublished - Mar 21 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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