Allelic loss and reduced expression of the ING3, a candidate tumor suppressor gene at 7q31, in human head and neck cancers

Abstract

Loss of heterozygosity (LOH) has been frequently detected at chromosome 7q31 region in human head and neck squamous cell carcinomas (HNSCC) and many other cancers, suggesting the existence of tumor suppressor genes (TSG). We analysed LOH at 7q31 region in 49 HNSCC by using six polymorphic microsatellite markers and found allelic deletion in 48% (22/46) of the informative cases. We detected two preferentially deleted regions, one is around D7S643 and the other around D7S486. When we rede®ned the map of 7q31 region according to the contiguous sequences, a recently identi®ed gene, ING3, was found in the proximity of D7S643. ING3 protein harbors the PHD domain highly homologous among ING family proteins, in which we previously found mutations in a related gene, ING1. As only one missense mutation of the ING3 gene was found in HNSCC, we examined the expression level. Reverse-transcription-PCR analysis demonstrated decreased or no expression of ING3 mRNA in 50% of primary tumors as compared with that of matched normal samples. Especially, about 63% of tongue and larynx tumors showed the decrease and a tendency of higher mortality was observed in cases with decreased ING3 expression. All these ®ndings suggest a possibility that the ING3 gene functions as a TSG in a subset of HNSCC.

Impairment of MLH1 and CDKN2A in oncogenesis of laryngeal cancer

“…The analysis of LOH indicated the involvement of a variety of genes in the development and progression of LSCC (Rainho et al, 2001;dos Reis et al, 2002;Fiedler et al, 2002;Gunduz et al, 2002). It is hypothesised that LSCC develops after the accumulation of six to 10 independent genetic events (Renan, 1993).…”

Detection of novel mRNA splice variants of human ING4 tumor suppressor gene

“…ING2 expression was reduced in colorectal, hepatocellular carcinoma, prostate, pancreatic, lung cancer and cutaneous melanoma (Nagashima et al, 2001;Lu et al, 2006;Okano et al, 2006). Allelic loss and reduced expression of ING3 have been also reported (Gunduz et al, 2002;Nagashima et al, 2003).…”

The tumor suppressor ING3 is degraded by SCFSkp2-mediated ubiquitin–proteasome system

“…It is ubiquitously expressed in normal human tissues and regulates gene transcription, cell cycle control and apoptosis (Nagashima et al, 2003). Distorted ING3 expression has been found in human head and neck squamous cell carcinomas (HNSCCs) and several lymphoma-derived cell lines (Gunduz et al, 2002(Gunduz et al, , 2008Fadlelmola et al, 2008). In melanoma cells, we have shown that ING3 promotes ultraviolet (UV)-induced apoptosis through the Fas/caspase-8-dependent pathway (Wang and Li, 2006).…”