Journal List > Korean J Urol > v.47(5) > 1069902

Kim, Yang, and Kim: Alterations in Calcium-Activated Potassium Channel Expressions in Human Prostate Cancer

Abstract

Purpose

Recent studies have shown that potassium (K+) and sodium channels are involved in prostate cell growth. However, a great many of the studies have been done in prostate cancer cell lines and there are only scant studies on prostate cancer and benign prostatic hypertrophy (BPH) tissue. The present study was aimed to evaluate the alterations of the calcium-activated K+ channel (KCa) expression in prostate cancer, and to compare them with the expression profiles in human BPH tissue to understand their potential role in the progression of prostate cancer.

Materials and Methods

The prostate tissues obtained from radical prostatectomy (n=10) and transurethral resection of the prostate (n=18) were quickly frozen in liquid nitrogen for the RNA measurements. The protein and mRNA levels of the KCa subtypes and connexins were measured by performing immunoblot analysis and reverse-transcription polymerase chain reaction, respectively.

Results

The mRNA levels of type 2 (SK2) and type 3 (SK3) small-conductance and large-conductance (BK) KCas in the prostate cancer tissues were decreased more than 50% compared with those in the BPH samples. In addition, the BK and SK2 protein levels in prostate cancer were also significantly lower than those in the BPH. As reported previously, the connexin 26 and 43 transcript signals in the prostate cancer were significantly reduced compared with those in the BPH samples.

Conclusions

These results suggest that the impaired expression of KCas may have a role in tumor progression via aberrant and uncontrolled prostate cell growth.

Figures and Tables

Fig. 1
Representative examples (upper panel) and densitometric analyses (lower panel) of the polymerase chain reaction (PCR) products for BK, IK, SK2 and SK3 are corrected with the β-actin in each sample. The values are expressed in arbitrary densitometric units (A.D.U.) as mean±SEM of the human prostate tissue with either benign prostatic hypertrophy (BPH) or prostate cancer (CaP). *p<0.05 and p<0.01 compared to BPH (Mann-Whitney test). BK, IK and SK denote large-, intermediate-, and small-conductance calcium activated potassium channels, respectively.
kju-47-548-g001
Fig. 2
Expressions of BK, SK2 and SK3 proteins corrected for β-actin in each sample. Values are shown in arbitrary units (A.U.) as mean±SEM of the human prostate tissue with either benign prostatic hypertrophy (BPH) or prostate cancer (CaP). *p<0.01 vs. BPH (Mann-Whitney test). BK and SK denote the large- and small-conductance calcium activated potassium channels, respectively.
kju-47-548-g002
Fig. 3
Representative examples (upper panel) and densitometric analyses (lower panel) of the PCR products for connexin (Cx) 26, Cx43 and Cx45 corrected for β-actin in each sample. The values are expressed in arbitrary densitometric units (A.D.U.) as mean±SEM of the human prostate tissue with either benign prostatic hypertrophy (BPH) or prostate cancer (CaP). *p<0.05 and p<0.01 compared to BPH (Mann-Whitney test).
kju-47-548-g003
Fig. 4
Expressions of connexin (Cx) 26 and Cx43 protein corrected for β-actin in each sample. Values are shown in arbitrary units (A.U.) as mean±SEM of human prostate tissue with either benign prostatic hypertrophy (BPH) or prostate cancer (CaP).
kju-47-548-g004
Table 1
Polymerase chain reaction (PCR) primer sequences of connexin and KCa channel subtypes
kju-47-548-i001

References

1. Gleave M, Miyake H, Chi K. Beyond simple castration: targeting the molecular basis of treatment resistance in advanced prostate cancer. Cancer Chemother Pharmacol. 2005. 56:Suppl 7. 47–57.
2. Pienta KJ, Smith DC. Advances in prostate cancer chemotherapy: a new era begins. CA Cancer J Clin. 2005. 55:300–318.
3. Abdul M, Hoosein N. Expression and activity of potassium ion channels in human prostate cancer. Cancer Lett. 2002. 186:99–105.
4. Laniado ME, Fraser SP, Djamgoz MB. Voltage-gated K(+) channel activity in human prostate cancer cell lines of markedly different metastatic potential: distinguishing characteristics of PC-3 and LNCaP cells. Prostate. 2001. 46:262–274.
5. Rybalchenko V, Prevarskaya N, Van Coppenolle F, Legrand G, Lemonnier L, Le Bourhis X, et al. Verapamil inhibits proliferation of LNCaP human prostate cancer cells influencing K+ channel gating. Mol Pharmacol. 2001. 59:1376–1387.
6. Skryma RN, Prevarskaya NB, Dufy-Barbe L, Odessa MF, Audin J, Dufy B. Potassium conductance in the androgen-sensitive prostate cancer cell line LNCaP: involvement in cell proliferation. Prostate. 1997. 33:112–122.
7. Diss JK, Archer SN, Hirano J, Fraser SP, Djamgoz MB. Expression profiles of voltage-gated Na(+) channel alpha-subunit genes in rat and human prostate cancer cell lines. Prostate. 2001. 48:165–178.
8. Fraser SP, Grimes JA, Djamgoz MB. Effects of voltage-gated ion channel modulators on rat prostatic cancer cell proliferation: comparison of strongly and weakly metastatic cell lines. Prostate. 2000. 44:61–76.
9. Grimes JA, Djamgoz MB. Electrophysiological characterization of voltage-gated Na+ current expressed in the highly metastatic Mat-LyLu cell line of rat prostate cancer. J Cell Physiol. 1998. 175:50–58.
10. Gopalakrishnan M, Shieh CC. Potassium channel subtypes as molecular targets for overactive bladder and other urological disorders. Expert Opin Ther Targets. 2004. 8:437–458.
11. Abdul M, Santo A, Hoosein N. Activity of potassium channel-blockers in breast cancer. Anticancer Res. 2003. 23:3347–3351.
12. Parihar AS, Coghlan MJ, Gopalakrishnan M, Shieh CC. Effects of intermediate-conductance Ca2+-activated K+ channel modulators on human prostate cancer cell proliferation. Eur J Pharmacol. 2003. 471:157–164.
13. Rane SG. The growth regulatory fibroblast IK channel is the prominent electrophysiological feature of rat prostatic cancer cells. Biochem Biophys Res Commun. 2000. 269:457–463.
14. Ashcroft FM. Ion channels and disease. 2000. San Diego: Academic Press;125–160.
15. Day ML, Pickering SJ, Johnson MH, Cook DI. Cell-cycle control of a large-conductance K+ channel in mouse early embryos. Nature. 1993. 365:560–562.
16. Gee J, Tanaka M, Grossman HB. Connexin 26 is abnormally expressed in bladder cancer. J Urol. 2003. 169:1135–1137.
17. Carruba G, Stefano R, Cocciadiferro L, Saladino F, Di Cristina A, Tokar E, et al. Intercellular communication and human prostate carcinogenesis. Ann N Y Acad Sci. 2002. 963:156–168.
18. Habermann H, Ray V, Habermann W, Prins GS. Alterations in gap junction protein expression in human benign prostatic hyperplasia and prostate cancer. J Urol. 2002. 167:655–660.
19. Grossman HB, Liebert M, Lee IW, Lee SW. Decreased connexin expression and intercellular communication in human bladder cancer cells. Cancer Res. 1994. 54:3062–3065.
20. van Baren MJ, Heutink P. The PCR suite. Bioinformatics. 2004. 20:591–593.
21. Tsai H, Werber J, Davia MO, Edelman M, Tanaka KE, Melman A, et al. Reduced connexin 43 expression in high grade, human prostatic adenocarcinoma cells. Biochem Biophys Res Commun. 1996. 227:64–69.
22. Mehta PP, Lokeshwar BL, Schiller PC, Bendix MV, Ostenson RC, Howard GA, et al. Gap-junctional communication in normal and neoplastic prostate epithelial cells and its regulation by cAMP. Mol Carcinog. 1996. 15:18–32.
23. Hossain MZ, Jagdale AB, Ao P, LeCiel C, Huang RP, Boynton AL. Impaired expression and posttranslational processing of connexin43 and downregulation of gap junctional communication in neoplastic human prostate cells. Prostate. 1999. 38:55–59.
24. Govindarajan R, Zhao S, Song XH, Guo RJ, Wheelock M, Johnson KR, et al. Impaired trafficking of connexins in androgen-independent human prostate cancer cell lines and its mitigation by alpha-catenin. J Biol Chem. 2002. 277:50087–50097.
25. Tanaka M, Grossman HB. Connexin 26 induces growth suppression, apoptosis and increased efficacy of doxorubicin in prostate cancer cells. Oncol Rep. 2004. 11:537–541.
TOOLS
Similar articles