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Expression of candidate tumor suppressor gene ING2 is lost in non-small cell lung carcinoma
Damien Ythier1, Elisabeth Brambilla, Romuald Binet
1Molecular Basis of Lung Cancer Progression, INSERM U823, Albert Bonniot Institute, 38706 La Tronche Cedex, France.
Abstract:
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.
Insights
Loss of ING2 gene expression is common in non-small cell lung cancer (NSCLC), particularly adenocarcinoma. This downregulation may contribute to lung tumorigenesis independently of p53.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- ING2 functions as a tumor suppressor gene, regulating cell cycle, apoptosis, and senescence.
- Loss of ING2 expression correlates with increased genome instability.
- The role of ING2 in non-small cell lung cancer (NSCLC) pathogenesis requires further investigation.
Purpose of the Study:
- To investigate the expression status of ING2 in NSCLC.
- To explore potential mechanisms underlying ING2 downregulation in NSCLC.
- To assess the relationship between ING2 expression and clinicopathological features.
Main Methods:
- Immunohistochemistry (IHC) was used to evaluate ING2 protein expression in 120 NSCLC samples.
- Quantitative RT-PCR was employed to measure ING2 mRNA levels.
- Analysis of gene mutations, loss of heterozygosity, single nucleotide polymorphisms (SNPs), and promoter methylation was performed.
Main Results:
- ING2 protein was downregulated in over 50% of NSCLC cases, with higher prevalence in adenocarcinoma (68%) than squamous cell carcinoma (45%).
- Loss of ING2 expression was observed in early-stage tumors and was not linked to gender, age, or survival.
- Mechanisms for downregulation include decreased mRNA levels, potentially influenced by a common silent SNP, but not LOH, mutations, or promoter methylation.
- No correlation was found between ING2 and p53 expression levels.
Conclusions:
- Downregulation of ING2 is frequent in NSCLC and may contribute to lung tumorigenesis.
- ING2 loss in NSCLC appears to be independent of p53 status.
- Further research into the mechanisms of ING2 regulation and its functional role in lung cancer is warranted.
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