Skip to main content
Erschienen in: Tumor Biology 4/2014

01.04.2014 | Research Article

Truncation of inhibitor of growth family protein 5 effectively induces senescence, but not apoptosis in human tongue squamous cell carcinoma cell line

verfasst von: Lin Qi, Yang Zhang

Erschienen in: Tumor Biology | Ausgabe 4/2014

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
3.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
4.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
5.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
6.
Zurück zum Zitat 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.PubMed 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.PubMed
7.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
8.
Zurück zum Zitat Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961;25:585–621.PubMedCrossRef Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961;25:585–621.PubMedCrossRef
9.
Zurück zum Zitat Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345:458–60.PubMedCrossRef Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345:458–60.PubMedCrossRef
11.
Zurück zum Zitat Pazolli E, Stewart SA. Senescence: the good the bad and the dysfunctional. Curr Opin Genet Dev. 2008;18:42–7.PubMedCrossRef Pazolli E, Stewart SA. Senescence: the good the bad and the dysfunctional. Curr Opin Genet Dev. 2008;18:42–7.PubMedCrossRef
12.
Zurück zum Zitat 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.PubMed 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.PubMed
13.
Zurück zum Zitat 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
14.
Zurück zum Zitat Unoki M, Kumamoto K, Takenoshita S, Harris CC. Reviewing the current classification of inhibitor of growth family proteins. Cancer Sci. 2009;100:1173–9.PubMedCentralPubMedCrossRef Unoki M, Kumamoto K, Takenoshita S, Harris CC. Reviewing the current classification of inhibitor of growth family proteins. Cancer Sci. 2009;100:1173–9.PubMedCentralPubMedCrossRef
15.
16.
Zurück zum Zitat 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.PubMedCentralPubMed 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.PubMedCentralPubMed
17.
Zurück zum Zitat 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.CrossRef 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.CrossRef
18.
Zurück zum Zitat 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
19.
Zurück zum Zitat 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
20.
Zurück zum Zitat 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
Metadaten
Titel
Truncation of inhibitor of growth family protein 5 effectively induces senescence, but not apoptosis in human tongue squamous cell carcinoma cell line
verfasst von
Lin Qi
Yang Zhang
Publikationsdatum
01.04.2014
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 4/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1410-y

Weitere Artikel der Ausgabe 4/2014

Tumor Biology 4/2014 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.