51147

ING4

inhibitor of growth family, member 4;ING4;inhibitor of growth family, member 4

brain my036 protein|candidate tumor suppressor p33 ING1 homolog|inhibitor of growth protein 4

12p13.31

protein-coding

ING4 is a novel tumor suppressor which is downregulated in a number of cancers. In this study, we investigated the role of ING4 in tumor angiogenesis in colorectal carcinoma (CRC) patients. Semi-quantitative RT-PCR, western blots, and immunohistochemistry were used to determine ING4 mRNA and protein expression in CRC and normal tissue from 60 CRC specimens and 30 colonic adenoma specimens. The correlation between ING4 expression and clinical stage, histological grade as well as lymph node metastasis was evaluated. Immunohistochemistry was performed to explore the correlation between ING4 expression and microvessel density (MVD) in CRC. CRC tissue had significantly lower levels of ING4 mRNA and protein compared to colonic adenoma and normal intestinal tissue. Immunostaining showed ING4 expression in 38 (63.3 %), 30 (100 %), and 60 (100 %) cases of normal colonic mucosa, adenoma, and normal intestinal mucosal tissue, respectively. Lower ING4 levels correlated with higher clinical stage and histological grade. ING4 mRNA and protein levels were significantly lower in CRC patients with lymph node metastasis compared to patients without lymph node metastasis (0.41 +/- 0.30 vs. 0.91 +/- 0.29 and 0.60 +/- 0.21 vs. 0.87 +/- 0.27, respectively; p < 0.001). Importantly, ING4 mRNA and protein levels were negatively correlated with MVD in CRC patients (p < 0.001). Our data suggest that ING4 levels are a potential biomarker of CRC progression and that ING4 may inhibit tumor growth by modulating angiogenesis in CRC.

AIMS: tumour suppressor ING4 is one of ING family genes, which are involved in cell cycle arrest, gene transcription regulation, DNA repair and apoptosis. ING4 inhibition has been reported in various tumours, including gliomas, breast tumours, and stomach adenocarcinoma. The aim was to evaluate ING4 expression in lung cancers. METHOD AND RESULTS: By immunohistochemistry of 246 lung tumour tissues, reduced ING4 nuclear and cytoplasmic expression were both revealed in lung cancer and associated with tumour grade. Interestingly, compared with normal tissues, we found more tumours with ING4 expression in the cytoplasm higher than in the nucleus. Nuclear ING4 inhibition correlated with the tumour stage and lymph node metastasis. Consistent with these findings, semiquantitative reverse transcriptase-polymerase chain reaction and Western blotting demonstrated decreased ING4 mRNA and expression in 100% (50/50) tumour tissues. Furthermore, ING4 expression was lower in grade III than in grades I-II tumours. Reduced ING4 mRNA correlated with lymph node metastasis. CONCLUSIONS: Our results indicate that overall inhibition of ING4 expression and ING4 expression higher in cytoplasm than in nucleus of tumour cells may be involved in the initiation and progression of lung cancers, and thus, analysis for ING4 expression may be useful as a clinical diagnostic and prognostic tool for lung cancer.