Abstract
In these studies, inhibitor of growth protein 5 (ING5) and various fragments of it were overexpressed in the human tongue squamous cell carcinoma cell line, HSC-3. The roles of ING5 in HSC-3 cells were then identified in vitro. Our results indicate that intact ING5 can inhibit proliferation and induce apoptosis in HSC-3 cells. Moreover, two truncated fragments of ING5 (aa 1-184 and aa 107-226) can induce cellular senescence. To analyze the signaling pathway involved, western blotting was performed. In these assays, two truncated fragments of ING5 were found to inhibit the cyclin E and CDK2 expression. These results are consistent with the S phase arrest observed with the overexpression of truncated ING5. However, the mechanisms of ING5-induced cellular senescence remain unclear, and extensive investigations are required in future studies.
Similar content being viewed by others
References
He GH, Helbing CC, Wagner MJ, Sensen CW, Riabowol K. Phylogenetic analysis of the ING family of PHD finger proteins. Mol Biol Evol. 2005;22:104–16.
Coles AH, Jones SN. The ING gene family in the regulation of cell growth and tumorigenesis. J Cell Physiol. 2009;218:45–57.
Russell M, Berardi P, Gong W, Riabowol K. Grow-ING, Age-ING and Die-ING: ING proteins link cancer, senescence and apoptosis. Exp Cell Res. 2006;312:951–61.
Soliman MA, Riabowol K. After a decade of study-ING, a PHD for a versatile family of proteins. Trends Biochem Sci. 2007;32:509–19.
Doyon Y, Cayrou C, Ullah M, Landry AJ, Côté V, Selleck W, et al. ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell. 2006;21:51–64.
Shiseki M, Nagashima M, Pedeux RM, Kitahama-Shiseki M, Miura K, Okamura S, et al. p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity. Cancer Res. 2003;63:2373–8.
Cengiz B, Gunduz E, Gunduz M, Beder LB, Tamamura R, Bagci C, et al. Tumor-specific mutation and downregulation of ING5 detected in oral squamous cell carcinoma. Int J Cancer. 2010;127:2088–94.
Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961;25:585–621.
Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345:458–60.
Rodier F, Campisi J. Four faces of cellular senescence. J Cell Biol. 2011;192:547–56.
Pazolli E, Stewart SA. Senescence: the good the bad and the dysfunctional. Curr Opin Genet Dev. 2008;18:42–7.
Sun X, Liu B, Wang J, Li J, Ji WY. Inhibition of p21-activated kinase 4 expression suppresses the proliferation of Hep-2 laryngeal carcinoma cells via activation of the ATM/Chk1/2/p53 pathway. Int J Oncol. 2013;42:683–9.
Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A. 1995;92:9363–7.
Unoki M, Kumamoto K, Takenoshita S, Harris CC. Reviewing the current classification of inhibitor of growth family proteins. Cancer Sci. 2009;100:1173–9.
Mathon NF, Lloyd AC. Cell senescence and cancer. Nat Rev Cancer. 2001;1:203–13.
Garkavtsev I, Riabowol K. Extension of the replicative life span of human diploid fibroblasts by inhibition of the p33ING1 candidate tumor suppressor. Mol Cell Biol. 1997;17:2014–9.
Schwarze SR, DePrimo SE, Grabert LM, Fu VX, Brooks JD, Jarrard DF. Novel pathways associated with bypassing cellular senescence in human prostate epithelial cells. J Biol Chem. 2002;17:14877–83.
Kumamoto K, Spillare EA, Fujita K, Horikawa I, Yamashita T, Appella E, et al. Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescence. Cancer Res. 2008;68:3193–203.
Iglesias-Bartolome R, Patel V, Cotrim A, Leelahavanichkul K, Molinolo AA, Mitchell JB, et al. mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis. Cell Stem Cell. 2012;11:401–14.
Rajarajacholan UK, Thalappilly S, Riabowol K. The ING1a tumor suppressor regulates endocytosis to induce cellular senescence via the Rb-E2F pathway. PLoS Biol. 2013;11:e1001502.
Acknowledgments
We appreciate the thoughtful advice of Yang Bai (China Medical University).
Conflicts of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Qi, L., Zhang, Y. Truncation of inhibitor of growth family protein 5 effectively induces senescence, but not apoptosis in human tongue squamous cell carcinoma cell line. Tumor Biol. 35, 3139–3144 (2014). https://doi.org/10.1007/s13277-013-1410-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-013-1410-y