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The 44 kDa Pim-1 kinase directly interacts with tyrosine kinase Etk/BMX and protects human prostate cancer cells from apoptosis induced by chemotherapeutic drugs

Oncogene volume 25, pages 70–78 (2006)Cite this article

Abstract

Protein kinase Pim-1 has been implicated in the development of hematopoietic and prostatic malignancies. Here, we present the evidence that two isoforms, the 44 and 33 kDa Pim-1, are expressed in all human prostate cancer cell lines examined. The subcellular localization of human 44 kDa Pim-1 is primarily on the plasma membrane, while the 33 kDa isoform is present in both the cytosol and nucleus in PCA cells. The 44 kDa Pim-1 contains the proline-rich motif at the N-terminus and directly binds to the SH3 domain of tyrosine kinase Etk. Such interaction leads to the activation of Etk kinase activity possibly by competing with the tumor suppressor p53. This is corroborated by the fact that overexpression of the 44 kDa Pim-1 in prostate cancer cells confers the resistance to chemotherapeutic drugs. Our results suggest that these two isoforms of Pim-1 kinase may regulate distinct substrates and the 44 kDa Pim-1 may play a more prominent role in drug resistance in prostate cancer cells.

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References

  • Aho TL, Sandholm J, Peltola KJ, Mankonen HP, Lilly M, Koskinen PJ . (2004). FEBS Lett 571: 43–49.

  • Amson R, Sigaux F, Przedborski S, Flandrin G, Givol D, Telerman A . (1989). Proc Natl Acad Sci USA 86: 8857–8861.

  • Breuer M, Slebos R, Verbeek S, van Lohuizen M, Wientjens E, Berns A . (1989). Nature 340: 61–63.

  • Chen R, Kim O, Li M, Xiong X, Guan JL, Kung HJ et al. (2001). Nat Cell Biol 3: 439–444.

  • Cuypers HT, Selten G, Quint W, Zijlstra M, Maandag ER, Boelens W et al. (1984). Cell 37: 141–150.

  • Dhanasekaran SM, Barrette TR, Ghosh D, Shah R, Varambally S, Kurachi K et al. (2001). Nature 412: 822–826.

  • Ellwood-Yen K, Graeber TG, Wongvipat J, Iruela-Arispe ML, Zhang J, Matusik R et al. (2003). Cancer Cell 4: 223–238.

  • Gregory CW, Johnson Jr RT, Mohler JL, French FS, Wilson EM . (2001). Cancer Res 61: 2892–2898.

  • Imasato Y, Xuan JW, Sakai H, Izawa JI, Saito Y, Chin JL et al. (2000). J Urol 164: 1819–1824.

  • Ishibashi Y, Maita H, Yano M, Koike N, Tamai K, Ariga H et al. (2001). FEBS Lett 506: 33–38.

  • Jiang T, Guo Z, Dai B, Kang M, Ann DK, Kung HJ et al. (2004). J Biol Chem 279: 50181–50189.

  • Kim O, Jiang T, Xie Y, Guo Z, Chen H, Qiu Y . (2004). Oncogene 23: 1838–1844.

  • Kim O, Yang J, Qiu Y . (2002). J Biol Chem 277: 30066–30071.

  • Koike N, Maita H, Taira T, Ariga H, Iguchi-Ariga SM . (2000). FEBS Lett 467: 17–21.

  • Leverson JD, Koskinen PJ, Orrico FC, Rainio EM, Jalkanen KJ, Dash AB et al. (1998). Mol Cell 2: 417–425.

  • Mochizuki T, Kitanaka C, Noguchi K, Muramatsu T, Asai A, Kuchino Y . (1999). J Biol Chem 274: 18659–18666.

  • Qiu Y, Robinson D, Pretlow TG, Kung HJ . (1998). Proc Natl Acad Sci USA 95: 3644–3649.

  • Saris CJ, Domen J, Berns A . (1991). EMBO J 10: 655–664.

  • Shirogane T, Fukada T, Muller JM, Shima DT, Hibi M, Hirano T . (1999). Immunity 11: 709–719.

  • Valdman A, Fang X, Pang ST, Ekman P, Egevad L . (2004). Prostate 60: 367–371.

  • van Lohuizen M, Verbeek S, Krimpenfort P, Domen J, Saris C, Radaszkiewicz T et al. (1989). Cell 56: 673–682.

  • von Lindern M, van Agthoven T, Hagemeijer A, Adriaansen H, Grosveld G . (1989). Oncogene 4: 75–79.

  • Wang S, Gao J, Lei Q, Rozengurt N, Pritchard C, Jiao J et al. (2003). Cancer Cell 4: 209–221.

  • Wang Z, Bhattacharya N, Mixter PF, Wei W, Sedivy J, Magnuson NS . (2002). Biochim Biophys Acta 1593: 45–55.

  • Yan B, Zemskova M, Holder S, Chin V, Kraft A, Koskinen PJ et al. (2003). J Biol Chem 278: 45358–45367.

  • Zhao T, Heyduk T, Eissenberg JC . (2001). J Biol Chem 276: 9512–9518.

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Acknowledgements

We would like to thank Dr CW Gregory for providing the CWR-R1 cells for our study. This work was supported in part by the NIH Grant (CA85380) and DOD Grant (DAMD17-03-1-0117) to YQ, DOD Postdoctoral Fellowship (W81XWH-04-1-0015) to ZG, and DOD Predoctoral Fellowship (PC050649) to KX.

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  1. Department of Pharmacology & Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD, USA

    Y Xie, K Xu, B Dai, Z Guo, T Jiang & Y Qiu

  2. Department of Epidemiology & Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    H Chen

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  1. Y Xie
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Correspondence to Y Qiu.

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Xie, Y., Xu, K., Dai, B. et al. The 44 kDa Pim-1 kinase directly interacts with tyrosine kinase Etk/BMX and protects human prostate cancer cells from apoptosis induced by chemotherapeutic drugs. Oncogene 25, 70–78 (2006). https://doi.org/10.1038/sj.onc.1209058

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