ARP2, a Novel Pro-apoptotic Protein Expressed in Epithelial Prostate Cancer LNCaP Cells and Epithelial Ovary CHO Transformed Cells

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Jan 28

PMID 24465888

Authors

Jaime Mas-Oliva

Enrique Navarro-Vidal

Juana Virginia Tapia-Vieyra

Affiliations

Soon will be listed here.

Abstract

Neoplastic epithelial cells generate the most aggressive types of cancers such as those located in the lung, breast, colon, prostate and ovary. During advanced stages of prostate cancer, epithelial cells are associated to the appearance of androgen-independent tumors, an apoptotic-resistant phenotype that ultimately overgrows and promotes metastatic events. We have previously identified and electrophysiologically characterized a novel Ca(2+)-permeable channel activated during apoptosis in the androgen-independent prostate epithelial cancer cell line, LNCaP. In addition, we reported for the first time the cloning and characterization of this channel-like molecule named apoptosis regulated protein 2 (ARP2) associated to a lethal influx of Ca(2+) in Xenopus oocytes. In the present study, LNCaP cells and Chinese hamster ovary cells (CHO cell line) transfected with arp2-cDNA are induced to undergo apoptosis showing an important impact on cell viability and activation of caspases 3 and 7 when compared to serum deprived grown cells and ionomycin treated cells. The subcellular localization of ARP2 in CHO cells undergoing apoptosis was studied using confocal microscopy. While apoptosis progresses, ARP2 initially localized in the peri-nuclear region of cells migrates with time towards the plasma membrane region. Based on the present results and those of our previous studies, the fact that ARP2 constitutes a novel cation channel is supported. Therefore, ARP2 becomes a valuable target to modulate the influx and concentration of calcium in the cytoplasm of epithelial cancer cells showing an apoptotic-resistant phenotype during the onset of an apoptotic event.

References

Raff M . Social controls on cell survival and cell death. Nature. 1992; 356(6368):397-400. DOI: 10.1038/356397a0. View

Williams G . Programmed cell death: apoptosis and oncogenesis. Cell. 1991; 65(7):1097-8. DOI: 10.1016/0092-8674(91)90002-g. View

Parekh A, Penner R . Store depletion and calcium influx. Physiol Rev. 1997; 77(4):901-30. DOI: 10.1152/physrev.1997.77.4.901. View

Orrenius S, Zhivotovsky B, Nicotera P . Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol. 2003; 4(7):552-65. DOI: 10.1038/nrm1150. View

Prevarskaya N, Skryma R, Shuba Y . Ca2+ homeostasis in apoptotic resistance of prostate cancer cells. Biochem Biophys Res Commun. 2004; 322(4):1326-35. DOI: 10.1016/j.bbrc.2004.08.037. View

Luo H, Moreau G, Levin N, Moore M . The human Prp8 protein is a component of both U2- and U12-dependent spliceosomes. RNA. 1999; 5(7):893-908. PMC: 1369814. DOI: 10.1017/s1355838299990520. View

Yuan T, Veeramani S, Lin F, Kondrikou D, Zelivianski S, Igawa T . Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells. Endocr Relat Cancer. 2006; 13(1):151-67. DOI: 10.1677/erc.1.01043. View

Vanoverberghe K, Vanden Abeele F, Mariot P, Lepage G, Roudbaraki M, Bonnal J . Ca2+ homeostasis and apoptotic resistance of neuroendocrine-differentiated prostate cancer cells. Cell Death Differ. 2003; 11(3):321-30. DOI: 10.1038/sj.cdd.4401375. View

Vaux D, Strasser A . The molecular biology of apoptosis. Proc Natl Acad Sci U S A. 1996; 93(6):2239-44. PMC: 39779. DOI: 10.1073/pnas.93.6.2239. View

10.

Berridge M . Capacitative calcium entry. Biochem J. 1995; 312 ( Pt 1):1-11. PMC: 1136219. DOI: 10.1042/bj3120001. View

11.

McCaffrey L, Macara I . Epithelial organization, cell polarity and tumorigenesis. Trends Cell Biol. 2011; 21(12):727-35. DOI: 10.1016/j.tcb.2011.06.005. View

12.

Chung L, Hsieh C, Law A, Sung S, Gardner T, Egawa M . New targets for therapy in prostate cancer: modulation of stromal-epithelial interactions. Urology. 2003; 62(5 Suppl 1):44-54. DOI: 10.1016/s0090-4295(03)00796-9. View

13.

Bruckheimer E, Gjertsen B, McDonnell T . Implications of cell death regulation in the pathogenesis and treatment of prostate cancer. Semin Oncol. 1999; 26(4):382-98. View

14.

Chung L, Davies R . Prostate epithelial differentiation is dictated by its surrounding stroma. Mol Biol Rep. 1996; 23(1):13-9. DOI: 10.1007/BF00357069. View

15.

Martikainen P, Kyprianou N, Tucker R, Isaacs J . Programmed death of nonproliferating androgen-independent prostatic cancer cells. Cancer Res. 1991; 51(17):4693-700. View

16.

Nicotera P, Bellomo G, Orrenius S . Calcium-mediated mechanisms in chemically induced cell death. Annu Rev Pharmacol Toxicol. 1992; 32:449-70. DOI: 10.1146/annurev.pa.32.040192.002313. View

17.

Flourakis M, Lehenkyi V, Beck B, Raphael M, Vandenberghe M, Abeele F . Orai1 contributes to the establishment of an apoptosis-resistant phenotype in prostate cancer cells. Cell Death Dis. 2011; 1:e75. PMC: 3032347. DOI: 10.1038/cddis.2010.52. View

18.

Skryma R, Mariot P, Bourhis X, Coppenolle F, Shuba Y, Vanden Abeele F . Store depletion and store-operated Ca2+ current in human prostate cancer LNCaP cells: involvement in apoptosis. J Physiol. 2000; 527 Pt 1:71-83. PMC: 2270062. DOI: 10.1111/j.1469-7793.2000.00071.x. View

19.

Bursch W, Oberhammer F, Schulte-Hermann R . Cell death by apoptosis and its protective role against disease. Trends Pharmacol Sci. 1992; 13(6):245-51. DOI: 10.1016/0165-6147(92)90077-j. View

20.

NEGOESCU A . Apoptosis in cancer: therapeutic implications. Histol Histopathol. 2000; 15(1):281-97. DOI: 10.14670/HH-15.281. View