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Volume 37 Issue 4

Apr. 2010

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Article Contents

Article Navigation > Journal of Genetics and Genomics > 2010 > 37(4): 249-255

hSHIP induces S-phase arrest and growth inhibition in cervical cancer HeLa cells

doi: 10.1016/S1673-8527(09)60043-6

a
Cancer Research Center, Medical College, Xiamen University, 422 Siming South Road, Xiamen 361005, China
b
School of Life Science, Xiamen University, 422 Siming South Road, Xiamen 361005, China

More Information

Corresponding author: E-mail address: jhyan@xmu.edu.cn (Jianghua Yan)
Received Date: 2009-11-08
Accepted Date: 2010-02-07
Rev Recd Date: 2010-01-26

Available Online: 2010-05-01

Publish Date: 2010-04-20

Abstract

hSHIP, a human SH2-containing inositol-5-phosphatase, acts as a negative regulator of proliferation and survival in hematopoietic cells. Therefore, hSHIP may play a crucial role in suppression of cervical cancer HeLa cells. In this study, pcDNA3.1-hSHIP-GFP plasmid was constructed and transfected into HeLa cells with Lipofectamine2000, stably transfected HeLa cells were established and their responses were investigated by Flow cytometry, MTT, tumorigenicity in nude mice, RT-PCR and ELISA assays. The results showed that the expression of hSHIP significantly induced S-phase arrest, cell growth inhibition, and down-regulation of Akt1/2 mRNA and p-Akt in HeLa cells. Our study supports an important role for hSHIP in suppression of cervical cancer HeLa cells, which may prove to be a novel therapeutic option for non-hematopoietic cancers.
- SH2-containing inositol-5-phosphatase (SHIP),
- cell cycle,
- cell growth,
- PI3K/Akt,
- HeLa cells

References

[1]	Lioubin, M.N., Algate, P.A., Tsai, S. et al. p150Ship, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity Genes Dev., 10 (1996),pp. 1084-1095
[2]	Tu, Z., Ninos, J.M., Ma, Z. et al. Embryonic and hematopoietic stem cells express a novel SH2-containing inositol 5′-phosphatase isoform that partners with the Grb2 adapter protein Blood, 98 (2001),pp. 2028-2038
[3]	Aman, M.J., Lamkin, T.D., Okada, H. et al. The inositol phosphatase SHIP inhibits Akt/PKB activation in B cells J. Biol. Chem., 273 (1998),pp. 33922-33928
[4]	Hunter, M.G., Avalos, B.R. Phosphatidylinositol 3′-kinase and SH2-containing inositol phosphatase (SHIP) are recruited by distinct positive and negative growth-regulatory domains in the granulocyte colony-stimulating factor receptor J. Immunol., 160 (1998),pp. 4979-4987
[5]	Kim, C.H., Hangoc, G., Cooper, S. et al. Altered responsiveness to chemokines due to targeted disruption of SHIP J. Clin. Invest., 104 (1999),pp. 1751-1759
[6]	Liu, Q., Sasaki, T., Kozieradzki, I. et al. SHIP is a negative regulator of growth factor receptor-mediated PKB/Akt activation and myeloid cell survival Genes Dev., 13 (1999),pp. 786-791
[7]	Damen, J.E., Liu, L., Rosten, P. et al. The 145-kDa protein induced to associate with Shc by multiple cytokines is an inositol tetraphosphate and phosphatidylinositol 3,4,5-triphosphate 5-phosphatase Proc. Natl. Acad. Sci. USA, 93 (1996),pp. 1689-1693
[8]	Zhang, X., Majerus, P.W. Phosphatidylinositol signalling reactions Semin. Cell Dev. Biol., 9 (1998),pp. 153-160
[9]	Liu, L., Damen, J.E., Ware, M. et al. SHIP, a new player in cytokine-induced signalling Leukemia, 11 (1997),pp. 181-184
[10]	Boer, A.K., Drayer, A.L., Vellenga, E. Effects of overexpression of the SH2-containing inositol phosphatase SHIP on proliferation and apoptosis of erythroid AS-E2 cells Leukemia, 15 (2001),pp. 1750-1757
[11]	Malbec, O., Schmitt, C., Bruhns, P. et al. Src homology 2 domain-containing inositol 5-phosphatase 1 mediates cell cycle arrest by FcgammaRIIB J. Biol. Chem., 276 (2001),pp. 30381-30391
[12]	Phee, H., Jacob, A., Coggeshall, K.M. Enzymatic activity of the Src homology 2 domain-containing inositol phosphatase is regulated by a plasma membrane location J. Biol. Chem., 275 (2000),pp. 19090-19097
[13]	Helgason, C.D., Damen, J.E., Rosten, P. et al. Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology, and a shortened life span Genes Dev., 12 (1998),pp. 1610-1620
[14]	Daley, G.Q., Van Etten, R.A., Baltimore, D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome Science, 247 (1990),pp. 824-830
[15]	Elefanty, A.G., Hariharan, I.K., Cory, S. bcr-abl, the hallmark of chronic myeloid leukaemia in man, induces multiple haemopoietic neoplasms in mice EMBO J., 9 (1990),pp. 1069-1078
[16]	Heisterkamp, N., Jenster, G., ten Hoeve, J. et al. Acute leukaemia in bcr/abl transgenic mice Nature, 344 (1990),pp. 251-253
[17]	Kelliher, M.A., McLaughlin, J., Witte, O.N. et al. Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL Proc. Natl. Acad. Sci. USA, 87 (1990),pp. 6649-6653
[18]	Coffer, P.J., Woodgett, J.R. Molecular cloning and characterisation of a novel putative protein-serine kinase related to the cAMP-dependent and protein kinase C families Eur. J. Biochem., 201 (1991),pp. 475-481
[19]	Hidalgo, M., Rowinsky, E.K. The rapamycin-sensitive signal transduction pathway as a target for cancer therapy Oncogene, 19 (2000),pp. 6680-6686
[20]	Osaki, M., Oshimura, M., Ito, H. PI3K-Akt pathway: its functions and alterations in human cancer Apoptosis, 9 (2004),pp. 667-676
[21]	Samuels, Y., Wang, Z., Bardelli, A. et al. Science, 304 (2004),p. 554
[22]	Shukla, S., Maclennan, G.T., Marengo, S.R. et al. Constitutive activation of P I3 K-Akt and NF-kappaB during prostate cancer progression in autochthonous transgenic mouse model Prostate, 64 (2005),pp. 224-239
[23]	Zhang, X.Y., Zhang, H.Y., Zhang, P.N. et al. Elevated phosphatidylinositol 3-kinase activation and its clinicopathological significance in cervical cancer Eur. J. Obstet. Gynecol. Reprod. Biol., 139 (2008),pp. 237-244
[24]	Levine, D.A., Bogomolniy, F., Yee, C.J. et al. Clin. Cancer Res., 11 (2005),pp. 2875-2878
[25]	Knobbe, C.B., Trampe-Kieslich, A., Reifenberger, G. Neuropathol. Appl. Neurobiol., 31 (2005),pp. 486-490
[26]	Oda, K., Stokoe, D., Taketani, Y. et al. Cancer Res., 65 (2005),pp. 10669-10673
[27]	Wang, J., Kuropatwinski, K., Hauser, J. et al. Mol. Cancer Ther., 6 (2007),pp. 1143-1150
[28]	Mancini, A., Koch, A., Wilms, R. et al. The SH2-containing inositol 5-phosphatase (SHIP)-1 is implicated in the control of cell-cell junction and induces dissociation and dispersion of MDCK cells Oncogene, 21 (2002),pp. 1477-1484
[29]	Xing, W., Hamaguchi, M. Effects of SHIP-1 on MMP2 secretion and invasion of SR3Y1 cells J. Genet. Genomics, 34 (2007),pp. 285-293
[30]	Kim, S., Kang, J., Hu, W. et al. Geldanamycin decreases Raf-1 and Akt levels and induces apoptosis in neuroblastomas Int. J. Cancer, 103 (2003),pp. 352-359
[31]	Altomare, D.A., Testa, J.R. Perturbations of the AKT signaling pathway in human cancer Oncogene, 24 (2005),pp. 7455-7464
[32]	Pines, J. Cyclins and cyclin-dependent kinases: theme and variations Adv. Cancer Res., 66 (1995),pp. 181-212

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沈阳化工大学材料科学与工程学院沈阳 110142

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