Calcium channel TRPV6 as a potential therapeutic target in estrogen receptor-negative breast cancer.
Calcium signaling is a critical regulator of cell proliferation. Elevated expression of calcium channels and pumps is a characteristic of some cancers, including breast cancer. We show that the plasma membrane calcium channel TRPV6, which is highly selective for Ca(2+), is overexpressed in some breast cancer cell lines. Silencing of TRPV6 expression in a breast cancer cell line with increased endogenous TRPV6 expression leads to a reduction in basal calcium influx and cellular proliferation associated with a reduction in DNA synthesis. TRPV6 gene amplification was identified as one mechanism of TRPV6 overexpression in a subset of breast cancer cell lines and breast tumor samples. Analysis of two independent microarray expression datasets from breast tumor samples showed that increased TRPV6 expression is a feature of estrogen receptor (ER)-negative breast tumors encompassing the basal-like molecular subtype, as well as HER2-positive tumors. Breast cancer patients with high TRPV6 levels had decreased survival compared with patients with low or intermediate TRPV6 expression. Our findings suggest that inhibitors of TRPV6 may offer a novel therapeutic strategy for the treatment of ER-negative breast cancers.
The University of Queensland, School of Pharmacy, Brisbane, Queensland, Australia, 4072.
Amelia A
AA
Peters
Peter T
PT
Simpson
Johnathon J
JJ
Bassett
Jane M
JM
Lee
Leonard
L
Da Silva
Lynne E
LE
Reid
Sarah
S
Song
Marie-Odile
MO
Parat
Sunil R
SR
Lakhani
Paraic A
PA
Kenny
Sarah J
SJ
Roberts-Thomson
Gregory R
GR
Monteith
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002452:Cell Count; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D011960:Receptors, Estrogen / Q000378:metabolism*; D016019:Survival Analysis; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
D015220:Calcium Channels; D011960:Receptors, Estrogen; D050916:TRPV Cation Channels; C422827:TRPV6 protein, human; D002118:Calcium