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pRb and p16 protein alterations in human oral tumorigenesis
P Pande1, M Mathur, N K Shukla
1Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Abstract:
Cyclin dependent kinase inhibitor 2/multiple tumour suppressor gene 1 (CDKN2/MTS1) and retinoblastoma (Rb) tumour suppressor genes play important roles in the regulation of the cell cycle. The protein products of these genes p16INK4 (p16) and pRb, respectively, like p53 protein inhibit progression from G1 to S phase. p16 exerts its function through inhibition of CDK4-mediated phosphorylation of pRb. The pRb/p16 pathway is a critical target for molecular aberration at the G1-S checkpoint in a wide range of primary human tumours. The expression of p16 and pRb proteins was analyzed by immunohistochemistry in 35 cases of oral squamous cell carcinomas (SCCs), 22 cases of premalignant oral lesions and 30 normal oral tissues. Lack of pRb expression was observed in 23/35 (66%) oral SCCs and 14/22 (64%) premalignant lesions. Lack of p16 expression was observed in 22/35 (63%) oral SCCs and 13/22 (59%) premalignant lesions. Weak p16 and pRb immunoreactivities were observed in normal oral mucosal epithelium. The status of p16 and pRb was correlated with clinicopathological characteristics of the patients. Alteration in p16 expression showed significant correlation with tumour staging and progression (P = 0.024). Alteration in pRb/p16 expression correlated with heavy consumption of betel and tobacco. Our results suggest that alterations in the p16/pRb pathway are early events in oral tumorigenesis and may be involved in the development of betel- and tobacco-related oral malignancies.
Insights
Alterations in the p16/pRb pathway, crucial for cell cycle regulation, are early events in oral cancer development. Loss of p16INK4 (p16) and pRb expression is common in oral squamous cell carcinomas and premalignant lesions, linked to betel and tobacco use.
Area of Science:
- Molecular Biology
- Oncology
- Cell Cycle Regulation
Background:
- The cell cycle is tightly regulated by tumor suppressor genes, including CDKN2/MTS1 (p16INK4, p16) and Rb (pRb).
- The pRb/p16 pathway is a critical checkpoint (G1-S phase) frequently altered in human cancers.
- Understanding alterations in this pathway is vital for oral cancer research.
Purpose of the Study:
- To analyze the expression of p16 and pRb proteins in oral squamous cell carcinomas (SCCs), premalignant lesions, and normal oral tissues.
- To correlate the expression status of p16 and pRb with clinicopathological characteristics and habits like betel and tobacco consumption.
- To investigate the role of p16/pRb pathway alterations in early oral tumorigenesis.
Main Methods:
- Immunohistochemistry was employed to assess p16 and pRb protein expression.
- Analysis was conducted on 35 oral SCCs, 22 premalignant oral lesions, and 30 normal oral tissues.
- Statistical correlation with clinicopathological data and patient habits was performed.
Main Results:
- A significant lack of pRb expression was observed in 66% of oral SCCs and 64% of premalignant lesions.
- Loss of p16 expression was noted in 63% of oral SCCs and 59% of premalignant lesions.
- Alterations in p16 expression correlated significantly with tumor staging and progression (P=0.024), and pRb/p16 alterations correlated with betel and tobacco consumption.
Conclusions:
- Alterations in the p16/pRb pathway are early events in oral tumorigenesis.
- The loss of p16 and pRb expression is a common molecular event in oral squamous cell carcinomas and premalignant lesions.
- These pathway alterations may be involved in the development of betel- and tobacco-related oral malignancies.