TRPC channels and their splice variants are essential for promoting human ovarian cancer cell proliferation and tumorigenesis

Bo Zeng, Cunzhong Yuan, Xingsheng Yang, Stephen Atkin, Shang Zhong Xu

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

TRPC channels are Ca2+-permeable cationic channels controlling Ca2+ influx response to the activation of G protein-coupled receptors and protein tyrosine kinase pathways or the depletion of Ca2+ stores. Here we aimed to investigate whether TRPC can act as the potential therapeutic targets for ovarian cancer. The mRNAs of TRPC1, TRPC3, TRPC4 and TRPC6 were detected in human ovarian adenocarcinoma. The spliced variants of TRPC1β, TRPC3a, TRPC4β, TRPC4γ, and TRPC6 with exon 3 and 4 deletion were highly expressed in the ovarian cancer cells, and a novel spliced isoform of TRPC1 with exon 9 deletion (TRPC1E9del) was identified. TRPC proteins were also detected by Western blotting and immunostaining. The expression of TRPC1, TRPC3, TRPC4 and TRPC6 was significantly lower in the undifferentiated ovarian cancer cells, but all-trans retinoic acid up-regulated the gene expression of TRPCs. The expression level was correlated to the cancer differentiation grade. The non-selective TRPC channel blockers, 2-APB and SKF-96365, significantly inhibited the cell proliferation, whilst the increase of TRPC channel activity by trypsin promoted the cell proliferation. Transfection with siRNA targeting TRPC1, TRPC3, TRPC4 and TRPC6 or application of specific blocking antibodies targeting to TRPC channels inhibited the cell proliferation. On the contrary, overexpression of TRPC1, TRPC1E9del, TRPC3, TRPC4, and TRPC6 increased the cancer cell colony growth. These results suggest that TRPCs and their spliced variants are important for human ovarian cancer development and alteration of the expression or activity of these channels could be a new strategy for anticancer therapy.

Original languageEnglish
Pages (from-to)103-116
Number of pages14
JournalCurrent Cancer Drug Targets
Volume13
Issue number1
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Ovarian Neoplasms
Carcinogenesis
Cell Proliferation
Exons
1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
Blocking Antibodies
Receptor Protein-Tyrosine Kinases
G-Protein-Coupled Receptors
Tretinoin
Trypsin
Small Interfering RNA
Transfection
Neoplasms
Protein Isoforms
Adenocarcinoma
Western Blotting
Gene Expression
Messenger RNA
Therapeutics
Growth

Keywords

  • Calcium channels
  • Ovarian cancer
  • Proliferation
  • SKOV3 cells
  • TRPC

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Cancer Research

Cite this

TRPC channels and their splice variants are essential for promoting human ovarian cancer cell proliferation and tumorigenesis. / Zeng, Bo; Yuan, Cunzhong; Yang, Xingsheng; Atkin, Stephen; Xu, Shang Zhong.

In: Current Cancer Drug Targets, Vol. 13, No. 1, 2013, p. 103-116.

Research output: Contribution to journalArticle

@article{e4e030e09f664b788116101186173ed0,
title = "TRPC channels and their splice variants are essential for promoting human ovarian cancer cell proliferation and tumorigenesis",
abstract = "TRPC channels are Ca2+-permeable cationic channels controlling Ca2+ influx response to the activation of G protein-coupled receptors and protein tyrosine kinase pathways or the depletion of Ca2+ stores. Here we aimed to investigate whether TRPC can act as the potential therapeutic targets for ovarian cancer. The mRNAs of TRPC1, TRPC3, TRPC4 and TRPC6 were detected in human ovarian adenocarcinoma. The spliced variants of TRPC1β, TRPC3a, TRPC4β, TRPC4γ, and TRPC6 with exon 3 and 4 deletion were highly expressed in the ovarian cancer cells, and a novel spliced isoform of TRPC1 with exon 9 deletion (TRPC1E9del) was identified. TRPC proteins were also detected by Western blotting and immunostaining. The expression of TRPC1, TRPC3, TRPC4 and TRPC6 was significantly lower in the undifferentiated ovarian cancer cells, but all-trans retinoic acid up-regulated the gene expression of TRPCs. The expression level was correlated to the cancer differentiation grade. The non-selective TRPC channel blockers, 2-APB and SKF-96365, significantly inhibited the cell proliferation, whilst the increase of TRPC channel activity by trypsin promoted the cell proliferation. Transfection with siRNA targeting TRPC1, TRPC3, TRPC4 and TRPC6 or application of specific blocking antibodies targeting to TRPC channels inhibited the cell proliferation. On the contrary, overexpression of TRPC1, TRPC1E9del, TRPC3, TRPC4, and TRPC6 increased the cancer cell colony growth. These results suggest that TRPCs and their spliced variants are important for human ovarian cancer development and alteration of the expression or activity of these channels could be a new strategy for anticancer therapy.",
keywords = "Calcium channels, Ovarian cancer, Proliferation, SKOV3 cells, TRPC",
author = "Bo Zeng and Cunzhong Yuan and Xingsheng Yang and Stephen Atkin and Xu, {Shang Zhong}",
year = "2013",
language = "English",
volume = "13",
pages = "103--116",
journal = "Current Cancer Drug Targets",
issn = "1568-0096",
publisher = "Bentham Science Publishers B.V.",
number = "1",

}

TY - JOUR

T1 - TRPC channels and their splice variants are essential for promoting human ovarian cancer cell proliferation and tumorigenesis

AU - Zeng, Bo

AU - Yuan, Cunzhong

AU - Yang, Xingsheng

AU - Atkin, Stephen

AU - Xu, Shang Zhong

PY - 2013

Y1 - 2013

N2 - TRPC channels are Ca2+-permeable cationic channels controlling Ca2+ influx response to the activation of G protein-coupled receptors and protein tyrosine kinase pathways or the depletion of Ca2+ stores. Here we aimed to investigate whether TRPC can act as the potential therapeutic targets for ovarian cancer. The mRNAs of TRPC1, TRPC3, TRPC4 and TRPC6 were detected in human ovarian adenocarcinoma. The spliced variants of TRPC1β, TRPC3a, TRPC4β, TRPC4γ, and TRPC6 with exon 3 and 4 deletion were highly expressed in the ovarian cancer cells, and a novel spliced isoform of TRPC1 with exon 9 deletion (TRPC1E9del) was identified. TRPC proteins were also detected by Western blotting and immunostaining. The expression of TRPC1, TRPC3, TRPC4 and TRPC6 was significantly lower in the undifferentiated ovarian cancer cells, but all-trans retinoic acid up-regulated the gene expression of TRPCs. The expression level was correlated to the cancer differentiation grade. The non-selective TRPC channel blockers, 2-APB and SKF-96365, significantly inhibited the cell proliferation, whilst the increase of TRPC channel activity by trypsin promoted the cell proliferation. Transfection with siRNA targeting TRPC1, TRPC3, TRPC4 and TRPC6 or application of specific blocking antibodies targeting to TRPC channels inhibited the cell proliferation. On the contrary, overexpression of TRPC1, TRPC1E9del, TRPC3, TRPC4, and TRPC6 increased the cancer cell colony growth. These results suggest that TRPCs and their spliced variants are important for human ovarian cancer development and alteration of the expression or activity of these channels could be a new strategy for anticancer therapy.

AB - TRPC channels are Ca2+-permeable cationic channels controlling Ca2+ influx response to the activation of G protein-coupled receptors and protein tyrosine kinase pathways or the depletion of Ca2+ stores. Here we aimed to investigate whether TRPC can act as the potential therapeutic targets for ovarian cancer. The mRNAs of TRPC1, TRPC3, TRPC4 and TRPC6 were detected in human ovarian adenocarcinoma. The spliced variants of TRPC1β, TRPC3a, TRPC4β, TRPC4γ, and TRPC6 with exon 3 and 4 deletion were highly expressed in the ovarian cancer cells, and a novel spliced isoform of TRPC1 with exon 9 deletion (TRPC1E9del) was identified. TRPC proteins were also detected by Western blotting and immunostaining. The expression of TRPC1, TRPC3, TRPC4 and TRPC6 was significantly lower in the undifferentiated ovarian cancer cells, but all-trans retinoic acid up-regulated the gene expression of TRPCs. The expression level was correlated to the cancer differentiation grade. The non-selective TRPC channel blockers, 2-APB and SKF-96365, significantly inhibited the cell proliferation, whilst the increase of TRPC channel activity by trypsin promoted the cell proliferation. Transfection with siRNA targeting TRPC1, TRPC3, TRPC4 and TRPC6 or application of specific blocking antibodies targeting to TRPC channels inhibited the cell proliferation. On the contrary, overexpression of TRPC1, TRPC1E9del, TRPC3, TRPC4, and TRPC6 increased the cancer cell colony growth. These results suggest that TRPCs and their spliced variants are important for human ovarian cancer development and alteration of the expression or activity of these channels could be a new strategy for anticancer therapy.

KW - Calcium channels

KW - Ovarian cancer

KW - Proliferation

KW - SKOV3 cells

KW - TRPC

UR - http://www.scopus.com/inward/record.url?scp=84875862265&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875862265&partnerID=8YFLogxK

M3 - Article

VL - 13

SP - 103

EP - 116

JO - Current Cancer Drug Targets

JF - Current Cancer Drug Targets

SN - 1568-0096

IS - 1

ER -