Cell cycle-dependent expression of HERG1 and HERG1B isoforms in tumor cells

Olivia Crociani, Leonardo Guasti, Manuela Balzi, Andrea Becchetti, Enzo Wanke, Massimo Olivotto, Randy S. Wymore, Annarosa Arcangeli

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Abstract

The role of K+ channel activity during cell cycle progression has become a research topic of considerable interest. Blocking of K+ channels inhibits the proliferation of many cell types, although the mechanism of this inhibition is unclear. There is speculation that K+ channels differentially regulate the electrical potential of the plasma membrane (Vm) during proliferation. We have demonstrated that in tumor cells the value of Vm is clamped to rather depolarized values by K+ channels belonging to the HERG family. We report here that tumor cell lines preferentially express the hergl gene and a truncated, N-deleted form that corresponds to herg1b. This alternative transcript is also expressed in human primary acute myeloid leukemias. Both HERG1 and HERG1B proteins are expressed on the plasma membrane of tumor cells and can form heterotetramers. The expression of HERG protein isoforms is strongly cell cycle-dependent, accounting for variations in HERG currents along the mitotic cycle. Moreover, the blocking of HERG channels dramatically impairs cell growth of HERG-bearing tumor cells. These results suggest that modulated expression of different K+ channels is the molecular basis of a novel mechanism regulating neoplastic cell proliferation.

Original languageEnglish
Pages (from-to)2947-2955
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number5
DOIs
StatePublished - 31 Jan 2003

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Tumors
Cell Cycle
Protein Isoforms
Cells
Neoplasms
Cell Proliferation
Cell Membrane
Cell membranes
Bearings (structural)
Tumor Cell Line
Acute Myeloid Leukemia
Cell proliferation
Cell growth
Growth
Genes
Research
Proteins

Cite this

Crociani, O., Guasti, L., Balzi, M., Becchetti, A., Wanke, E., Olivotto, M., ... Arcangeli, A. (2003). Cell cycle-dependent expression of HERG1 and HERG1B isoforms in tumor cells. Journal of Biological Chemistry, 278(5), 2947-2955. https://doi.org/10.1074/jbc.M210789200
Crociani, Olivia ; Guasti, Leonardo ; Balzi, Manuela ; Becchetti, Andrea ; Wanke, Enzo ; Olivotto, Massimo ; Wymore, Randy S. ; Arcangeli, Annarosa. / Cell cycle-dependent expression of HERG1 and HERG1B isoforms in tumor cells. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 5. pp. 2947-2955.
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Crociani, O, Guasti, L, Balzi, M, Becchetti, A, Wanke, E, Olivotto, M, Wymore, RS & Arcangeli, A 2003, 'Cell cycle-dependent expression of HERG1 and HERG1B isoforms in tumor cells', Journal of Biological Chemistry, vol. 278, no. 5, pp. 2947-2955. https://doi.org/10.1074/jbc.M210789200

Cell cycle-dependent expression of HERG1 and HERG1B isoforms in tumor cells. / Crociani, Olivia; Guasti, Leonardo; Balzi, Manuela; Becchetti, Andrea; Wanke, Enzo; Olivotto, Massimo; Wymore, Randy S.; Arcangeli, Annarosa.

In: Journal of Biological Chemistry, Vol. 278, No. 5, 31.01.2003, p. 2947-2955.

Research output: Contribution to journalArticle

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AU - Olivotto, Massimo

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Crociani O, Guasti L, Balzi M, Becchetti A, Wanke E, Olivotto M et al. Cell cycle-dependent expression of HERG1 and HERG1B isoforms in tumor cells. Journal of Biological Chemistry. 2003 Jan 31;278(5):2947-2955. https://doi.org/10.1074/jbc.M210789200