Sodium/proton exchanger isoform 1 regulates intracellular pH and cell proliferation in human ovarian cancer

Sanhueza, Carlos, Araos, Joaquín, Naranjo, Luciano, Toledo, Fernando, Beltran, Ana R., Ramirez, Marco A., Gutierrez, Jaime, Pardo, Fabián, Leiva, Andrea and Sobrevia, Luis (2017) Sodium/proton exchanger isoform 1 regulates intracellular pH and cell proliferation in human ovarian cancer. BBA - Molecular Basis of Disease, 1863 1: 81-91. doi:10.1016/j.bbadis.2016.10.013

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Author Sanhueza, Carlos
Araos, Joaquín
Naranjo, Luciano
Toledo, Fernando
Beltran, Ana R.
Ramirez, Marco A.
Gutierrez, Jaime
Pardo, Fabián
Leiva, Andrea
Sobrevia, Luis
Title Sodium/proton exchanger isoform 1 regulates intracellular pH and cell proliferation in human ovarian cancer
Journal name BBA - Molecular Basis of Disease   Check publisher's open access policy
ISSN 0925-4439
Publication date 2017-01-01
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.bbadis.2016.10.013
Open Access Status File (Author Post-print)
Volume 1863
Issue 1
Start page 81
End page 91
Total pages 11
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Collection year 2017
Language eng
Formatted abstract
Cancer cells generate protons (H+) that are extruded to the extracellular medium mainly via the Na+/H+ exchanger 1 (NHE1), which regulates intracellular pH (pHi) and cell proliferation. In primary cultures of human ascites-derived ovarian cancer cells (haOC) we assayed whether NHE1 was required for pHi modulation and cell proliferation. Human ovary expresses NHE1, which is higher in haOC and A2780 (ovarian cancer cells) compared with HOSE cells (normal ovarian cells). Basal pHi and pHi recovery (following a NH4Cl pulse) was higher in haOC and A2780, compared with HOSE cells. Zoniporide (NHE1 inhibitor) caused intracellular acidification and pHi recovery was independent of intracellular buffer capacity, but reduced in NHE1 knockdown A2780 cells. Zoniporide reduced the maximal proliferation capacity, cell number, thymidine incorporation, and ki67 (marker of proliferation) fluorescence in haOC cells. SLC9A1 (for NHE1) amplification associated with lower overall patient survival. In conclusion, NHE1 is expressed in human ovarian cancer where it has a pro-proliferative role. Increased NHE1 expression and activity constitute an unfavourable prognostic factor in these patients.
Keyword Cell proliferation
Human
NHE1
Ovarian cancer
PHi
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
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