Dysfunction of the p53 tumor suppressor pathway in head and neck cancer
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Published on: August 4, 2019
Mohammad O Hoque1, Hitoshi Kawamata, Koh-Ichi Nakashiro
1Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Tokushima 770-8504, Japan.
Abstract:
It is important to examine the abnormality of the entire p53 tumor suppressor pathway in head and neck cancer. We examined the mRNA expressions of p53 regulatory factors, p33ING1 and p14ARF, and a p53-target gene, p21WAF1 in head and neck cancer. Nine of 14 benign pleomorphic adenomas (PAs) and 7 of 8 malignant salivary gland tumors (MSGTs) expressed p33ING1 mRNA. Thirteen of 14 PAs expressed p14ARF mRNA, however, only 1 of 8 MSGTs expressed p14ARF mRNA. Eight of 14 PAs and 7 of 8 MSGTs expressed p21WAF1 mRNA. In salivary gland tumors, there was clear correlation between the expression of p33ING1 and p21WAF1 (p<0.0001, r2=0.53). However, there was no correlation between the expression of p14ARF and p21WAF1 (p=0.6543, r2=0.009). Twenty-six of 28 oral squamous cell carcinomas (SCCs) expressed p33ING1 mRNA. Nineteen of 28 oral SCCs expressed p14ARF mRNA. All of the oral SCCs expressed p21WAF1 mRNA. In oral SCCs, the expressions of both p33ING1 (p=0.009, r2=0.181) and p14ARF (p=0.0009, r2=0.271) correlated with the expression of p21WAF1. Interestingly, 24 of 26 oral SCCs (92%) showed either abnormality of p53 itself or loss of expression of p53 regulatory factors, p33ING or p14ARF. These results suggest that head and neck cancer often involve the dysfunction of p53 tumor suppressor pathway.
Insights
Head and neck cancers frequently show p53 pathway dysfunction. Researchers found that p53 regulatory factors, p33ING1 and p14ARF, and p21WAF1 gene expression are often abnormal in these cancers.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The p53 tumor suppressor pathway is crucial in preventing cancer development.
- Dysregulation of the p53 pathway is implicated in various human cancers, including head and neck malignancies.
- Understanding the specific alterations in this pathway is vital for therapeutic strategies.
Purpose of the Study:
- To investigate the expression patterns of key p53 regulatory factors (p33ING1, p14ARF) and a p53-target gene (p21WAF1) in head and neck cancers.
- To determine the correlation between the expression of these genes in different types of head and neck tumors.
- To assess the overall integrity of the p53 pathway in head and neck cancer.
Main Methods:
- Analysis of mRNA expression levels of p33ING1, p14ARF, and p21WAF1 in tissue samples.
- Utilized quantitative methods to assess gene expression in benign pleomorphic adenomas (PAs), malignant salivary gland tumors (MSGTs), and oral squamous cell carcinomas (SCCs).
- Statistical analysis to evaluate correlations between gene expression levels and the presence of p53 abnormalities.
Main Results:
- p33ING1 mRNA was expressed in most PAs, MSGTs, and oral SCCs.
- p14ARF mRNA was highly expressed in PAs but significantly downregulated in MSGTs and oral SCCs.
- p21WAF1 mRNA was expressed in most PAs, MSGTs, and all oral SCCs, correlating with p33ING1 and p14ARF in oral SCCs.
- A high percentage (92%) of oral SCCs exhibited abnormalities in p53, p33ING1, or p14ARF expression.
Conclusions:
- The p53 tumor suppressor pathway is frequently disrupted in head and neck cancers.
- Alterations in p33ING1 and p14ARF expression, alongside p21WAF1, are common in these malignancies.
- These findings highlight the importance of the p53 pathway's integrity in head and neck tumorigenesis.
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