Reduced ING1b gene expression plays an important role in carcinogenesis of non-small cell lung cancer patients.
OBJECTIVE
We performed a clinical study on ING1b gene expression and p53 gene status in relation to p53 target genes.


METHODS
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.
The Second Department of Surgery, Kagawa Medical University, Kagawa 761-0793, Japan.
Kotaro
K
Kameyama
Cheng-long
CL
Huang
Dage
D
Liu
Daiki
D
Masuya
Takashi
T
Nakashima
Shinichi
S
Sumitomo
Yuji
Y
Takami
Moritoshi
M
Kinoshita
Hiroyasu
H
Yokomise
D002277:Carcinoma; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D004587:Electrophoresis, Agar Gel; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D009687:Nuclear Proteins; D018807:Polymorphism, Single-Stranded Conformational; D014176:Protein Biosynthesis; D011506:Proteins / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)