Nuclear ING2 expression is reduced in osteosarcoma

Han,Xiao-Rui; Bai,Xi-Zhuang; Sun,Yu; Yang,Yan

doi:10.3892/or.2014.3458

Nuclear ING2 expression is reduced in osteosarcoma

Authors:
- Xiao-Rui Han
- Xi-Zhuang Bai
- Yu Sun
- Yan Yang
View Affiliations

Affiliations: Department of Joint Surgery and Sports Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: September 2, 2014 https://doi.org/10.3892/or.2014.3458
Pages: 1967-1972

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Osteosarcoma is a high-grade malignant bone tumor. Loss of inhibitor of growth 2 (ING2) expression has been demonstrated in numerous types of cancers. However, no study has shown the relationship between ING2 expression and osteosarcoma. In the present study, we confirmed that the levels of ING2 mRNA and protein were lower in cancer tissues than these levels in normal tissues. Loss of nuclear ING2 protein was significantly associated with a decreased survival time of patients. Osteosarcoma cells were transfected with ING2 protein without a nuclear localization signal or intact ING2 protein to examine the effects of exogenous expression of ING2 in vitro. Compared to the control cells, intact ING2-expressing cells exhibited increased apoptosis, G1 phase arrest and senescence. Taken together, these results suggest that ING2 acts as a tumor suppressor in osteosarcoma.

View Figures

View References

1	Bielack SS, Kempf-Bielack B, Delling G, et al: Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on Neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol. 20:776–790. 2002. View Article : Google Scholar
2	Meyers PA and Gorlick R: Osteosarcoma. Pediatr Clin North Am. 44:973–989. 1997. View Article : Google Scholar : PubMed/NCBI
3	Dai X, Ma W, He X and Jha RK: Review of therapeutic strategies for osteosarcoma, chondrosarcoma, and Ewing’s sarcoma. Med Sci Monit. 17:RA177–RHA190. 2011.
4	Watson RL, Spalding AC, Zielske SP, et al: GSK3beta and beta-catenin modulate radiation cytotoxicity in pancreatic cancer. Neoplasia. 12:357–365. 2010.PubMed/NCBI
5	Shi X, Hong T, Walter KL, et al: ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. Nature. 442:96–99. 2006.PubMed/NCBI
6	Nagashima M, Shiseki M, Miura K, et al: DNA damage-inducible gene p33ING2 negatively regulates cell proliferation through acetylation of p53. Proc Natl Acad Sci USA. 98:9671–9676. 2001. View Article : Google Scholar : PubMed/NCBI
7	Nagashima M, Shiseki M, Pedeux RM, et al: A novel PHD-finger motif protein, p47ING3, modulates p53-mediated transcription, cell cycle control and apoptosis. Oncogene. 22:343–350. 2003. View Article : Google Scholar : PubMed/NCBI
8	Shiseki M, Nagashima M, Pedeux RM, et al: p29ING4 and p28ING5 bind to p53 and p300 and enhance p53 activity. Cancer Res. 63:2373–2378. 2003.PubMed/NCBI
9	Guérillon C, Larrieu D and Pedeux R: ING1 and ING2: multifaceted tumor suppressor genes. Cell Mol Life Sci. 70:3753–3772. 2013.PubMed/NCBI
10	Borkosky SS, Gunduz M, Nagatsuka H, et al: Frequent deletion of ING2 locus at 4q35.1 associates with advanced tumor stage in head and neck squamous cell carcinoma. J Cancer Res Clin Oncol. 135:703–713. 2009. View Article : Google Scholar : PubMed/NCBI
11	Zhang HK, Pan K, Wang H, et al: Decreased expression of ING2 gene and its clinicopathological significance in hepatocellular carcinoma. Cancer Lett. 261:183–192. 2008. View Article : Google Scholar : PubMed/NCBI
12	Kumamoto K, Fujita K, Kurotani R, et al: ING2 is upregulated in colon cancer and increases invasion by enhanced MMP13 expression. Int J Cancer. 125:1306–1315. 2009. View Article : Google Scholar : PubMed/NCBI
13	Kyte J and Doolittle RF: A simple method for displaying the hydrophobic character of a protein. J Mol Biol. 157:105–132. 1982. View Article : Google Scholar
14	Hopp TP and Woods KR: Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci USA. 78:3824–3828. 1981. View Article : Google Scholar : PubMed/NCBI
15	Vihinen M, Torkkila E and Riikonen P: Accuracy of protein flexibility predictions. Proteins. 19:141–149. 1994. View Article : Google Scholar : PubMed/NCBI
16	Trier NH, Hansen PR and Houen G: Production and characterization of peptide antibodies. Methods. 56:136–144. 2012. View Article : Google Scholar : PubMed/NCBI
17	Dimri GP, Lee X, Basile G, et al: A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA. 92:9363–9367. 1995. View Article : Google Scholar : PubMed/NCBI
18	Jackson DA and Pombo A: Replicon clusters are stable units of chromosome structure: evidence that nuclear organization contributes to the efficient activation and propagation of S phase in human cells. J Cell Biol. 140:1285–1295. 1998. View Article : Google Scholar
19	Walzak AA, Veldhoen N, Feng X, Riabowol K and Helbing CC: Expression profiles of mRNA transcript variants encoding the human inhibitor of growth tumor suppressor gene family in normal and neoplastic tissues. Exp Cell Res. 314:273–285. 2008. View Article : Google Scholar
20	Ythier D, Brambilla E, Binet R, et al: Expression of candidate tumor suppressor gene ING2 is lost in non-small cell lung carcinoma. Lung Cancer. 69:180–186. 2010. View Article : Google Scholar : PubMed/NCBI
21	Lu F, Dai DL, Martinka M, Ho V and Li G: Nuclear ING2 expression is reduced in human cutaneous melanomas. Br J Cancer. 95:80–86. 2006. View Article : Google Scholar : PubMed/NCBI
22	Pedeux R, Sengupta S, Shen JC, et al: ING2 regulates the onset of replicative senescence by induction of p300-dependent p53 acetylation. Mol Cell Biol. 25:6639–6648. 2005. View Article : Google Scholar : PubMed/NCBI
23	Gozani O, Karuman P, Jones DR, et al: The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor. Cell. 114:99–111. 2003. View Article : Google Scholar : PubMed/NCBI
24	Pena PV, Davrazou F, Shi X, et al: Molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2. Nature. 442:100–103. 2006.PubMed/NCBI