Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jun;13(2):195-201.
doi: 10.1038/pcan.2009.55. Epub 2009 Dec 22.

Novel role for the transient receptor potential channel TRPM2 in prostate cancer cell proliferation

X Zeng  1 , S C Sikka, L Huang, C Sun, C Xu, D Jia, A B Abdel-Mageed, J E Pottle, J T Taylor, M Li
Affiliations

Novel role for the transient receptor potential channel TRPM2 in prostate cancer cell proliferation

X Zeng et al. Prostate Cancer Prostatic Dis. 2010 Jun.

Abstract

We have identified a novel function for a member of the transient receptor potential (TRP) protein super-family, TRPM2, in prostate cancer cell proliferation. TRPM2 encodes a non-selective cation-permeable ion channel. We found that selectively knocking down TRPM2 with the small interfering RNA technique inhibited the growth of prostate cancer cells but not of non-cancerous cells. The subcellular localization of this protein is also remarkably different between cancerous and non-cancerous cells. In BPH-1 (benign), TRPM2 protein is homogenously located near the plasma membrane and in the cytoplasm, whereas in the cancerous cells (PC-3 and DU-145), a significant amount of the TRPM2 protein is located in the nuclei in a clustered pattern. Furthermore, we have found that TRPM2 inhibited nuclear ADP-ribosylation in prostate cancer cells. However, TRPM2 knockdown-induced inhibition of proliferation is independent of the activity of poly(ADP-ribose) polymerases. We conclude that TRPM2 is essential for prostate cancer cell proliferation and may be a potential target for the selective treatment of prostate cancer.

PubMed Disclaimer

Figures

Figure 1
Figure 1
RT–PCR analysis of TRPM2 mRNA expression in prostate cancer cell lines. BPH, benign prostatic hyperplasia.
Figure 2
Figure 2
(a) Confocal microscopy showing the subcellular expression of TPRM2 protein in prostate cancer cell Lines (PC-3, DU-145), benign cells (BPH-1), and normal prostate epithelial cell line (RWPE-1). DU-145 is the 15th section of the z-series images (30 series). PC-3, BPH-1, and RWPE-1 are the 10th section of the z-series images (30 series). Red is propidium iodide (PI) label of nuclei and green is FITC fluorescence conjugated secondary antibody against TRPM2 antibody. Single arrows indicate the nuclear location of TRPM2 in cancer cells. Double arrow indicates plasma membrane expression of TRPM2 in BPH-1 cells. All images are the overlays of FITC and PI fluorescence. (b) Expression of TPRM2 proteins in both the nuclei and the remainders (whole cell preparation excluding nuclei) of prostate cancer cell lines (PC-3 and DU-145) and non-cancerous prostate epithelium cell lines (BPH and RWPE-1).
Figure 3
Figure 3
Selective inhibitory effect of siRNA-TRPM2 on prostate cancer cell proliferation. (a) Cell proliferation monitored in cell lines PC-3, DU-145, BPH-1, and RWPE-1 with WST-8 assay. The open square represents the data from untreated cells (control). The open triangle represents data from cells treated with 40 nM scrambled siRNA. The open circle represents the data from cells treated with 40 nM siRNA-TRPM2. N=3 for all groups. Error bar represents the standard deviation. *Indicates P<0.05 between siRNA-TRPM2 treatment and the two other groups. (b) RT–PCR showed that TRPM2 mRNA expression is inhibited by the siRNA-TRPM2 treatment in DU-145 and PC-3 2 days after the siRNA transfection. The sizes of PCR products are 293 bp and 234 bp for TRPM2 and GAPDH, respectively. (c) Western blot shows that TRPM2 protein expression is inhibited in PC-3 by 40 nM siRNA-TRPM2 treatment for 72 h. Repeated three times. siTRPM2: siRNA-TRPM2.
Figure 4
Figure 4
Effect of siRNA-TRPM2 on ADP-ribosylation in PC-3 cells. (a) Immunofluorescence indicating ADP-ribosylation in PC-3 cells transfected with no siRNA (control), scrambled siRNA, or siRNA-TRPM2. The magnification for all of the images is × 10. (b) ELISA measurement of ADP-ribosylation in PC-3 and BPH-1 cells. *Indicates P<0.01 of Student's t-test between the siRNA-TRPM2 treated and the control groups. (c) Dose-dependent toxic effect of UN1025 on PC-3 cells. (d) PC-3 cell proliferation of under the conditions of 40 nM siRNA-TRPM2 treatment and co-treatment with siRNA-TRPM2 and 100 μM UN1025. #Indicates P<0.05 of Student's t-test between the siRNA-TRPM2 or UN1025+siRNA-TRPM2 treated and the control groups.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Pervarskaya N, Flourakis M, Bidaux G, Thebault S, Skryma R. Differential role of TRP channels in prostate cancer. Biochem Soc Trans. 2007;35:133–135. - PubMed
    1. Ishii M, Oyama A, Hagiwara T, Miyazaki A, Mori Y, Kiuchi Y, et al. Facilitation of H2O2-induced A172 human glioblastoma cell death by insertion of oxidative stress-sensitive TRPM2 channels. Anticancer Res. 2007;27:3987–3992. - PubMed
    1. Orfanelli U, Wenke A-K, Doglioni C, Russo V, Bosserhoff AK, Lavorgna G. Identification of novel sense and antisense transcription at the TRPM2 locus in cancer. Cell Res. 2008;18:1128–1140. - PubMed
    1. Clapham DE. TRP channels as cellular sensors. Nature. 2003;426:517–524. - PubMed
    1. Perraud AL, Schmitz C, Scharenberg AM. TRPM2 Ca2+ permeable cation channels: from gene to biological function. Cell Calcium. 2003;33:519–531. - PubMed

Publication types

MeSH terms