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Reduced ING1b Gene Expression Plays an Important Role in Carcinogenesis of Non-Small Cell Lung Cancer Patients

The Second Department of Surgery, Kagawa Medical University, Kagawa 761-0793, Japan [K. K., C-l. H., D. L., D. M., T. N., H. Y.]; Department of Thoracic Surgery, Japanese Red Cross Society Wakayama Medical Center, Wakayama 640-8558, Japan [S. S.]; and Gene Diagnostic Center, Otsuka Assay Laboratory, Otsuka Pharmaceutical Co., Ltd., Tokushima 771-0195, Japan [Y. T., M. K.]

Purpose: We performed a clinical study on ING1b gene expression and p53 gene status in relation to p53 target genes.

Experimental Design: Eighty-eight tumors from surgically treated non-small cell lung cancer (NSCLC) patients were studied. PCR-single-strand conformational polymorphism after sequencing was performed to investigate ING1 and p53 gene status. Quantitative reverse transcription-PCR was performed to evaluate the gene expression of ING1b, p21, and bax. The results of p21 and bax expression were confirmed with immunohistochemistry.

Results: Only two carcinomas (2.3%) had nonmissense mutations of ING1b. Thirty-seven carcinomas (42.0%) had reduced ING1b gene expression. Thirty-seven carcinomas (42.0%) had mutations of p53. In total, 63 carcinomas (71.6%) had either reduced ING1b expression or mutant p53. The p21 gene expression ratio was significantly lower in the ING1b-reduced tumors than in the ING1b-positive tumors (P = 0.0029). Similarly, the bax gene expression ratio was significantly lower in the ING1b-reduced tumors than in the ING1b-positive tumors (P < 0.0001), and it was also significantly lower in tumors that had either reduced ING1b expression or mutant p53 than in tumors that had both positive ING1b expression and wild-type p53 (P = 0.0331).

Conclusions: Reduction of ING1b gene expression was associated with reduced p21 and bax gene expression in NSCLCs. The present study is the first clinical report to confirm the positive role of ING1b in regulating p21 and bax gene expression. ING1b might be one of the tumor suppressor genes that could play a role in carcinogenesis in NSCLC patients.

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