Expression of candidate tumor suppressor gene ING2 is lost in non-small cell lung carcinoma.
ING2 is a candidate tumor suppressor gene involved in cell cycle control, apoptosis and senescence. Furthermore, we have recently shown that loss of ING2 expression is associated with increased genome instability. We investigated its status in a series of 120 non-small cell lung cancer (NSCLC) by using immunohistochemistry (IHC). The results showed that ING2 protein expression is downregulated in more than 50% of NSCLC, with a higher frequency in adenocarcinoma (ADK) as compared to squamous cell carcinoma (SCC) (68% versus 45%, P=0.021). Loss of ING2 expression occurs in a high proportion of tumors from stage I and was not associated with patient's gender, age and 5-year survival. When investigating the possible mechanisms responsible for the decrease of ING2 expression, we did not observe any loss of heterozygosity or mutation in the ING2 gene. However, in 95% of the cases examined, we identified a silent single nucleotide polymorphism (SNP). By using quantitative RT-PCR, we found that ING2 loss of expression may be due to the decrease of its mRNA level. Analysis of CpG islands present in the promoter region of the ING2 gene did not allow for the detection of methylation. Mechanistically, although p53 can regulate ING2 transcription and ING2 enhances p53 activity, no correlation between ING2 and p53 IHC status was observed. Overall, these results indicate that loss of ING2 expression could contribute to lung tumorigenesis independently of p53.
Ythier
Damien
D
Molecular Basis of Lung Cancer Progression, INSERM U823, Albert Bonniot Institute, 38706 La Tronche Cedex, France.
Brambilla
Elisabeth
E
Binet
Romuald
R
Nissou
Damien
D
Vesin
Aurélien
A
de Fraipont
Florence
F
Moro-Sibilot
Denis
D
Lantuejoul
Sylvie
S
Brambilla
Christian
C
Gazzeri
Sylvie
S
Pedeux
Rémy
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
D018398:Homeodomain Proteins; C444654:ING2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins