Related Experiment Video
Updated: Oct 7, 2026

Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines
Published on: August 21, 2019
The exogenous wild-type p14ARF gene induces growth arrest and promotes radiosensitivity in human lung cancer cell
1Department of Radiotherapy, Cancer Institute and Cancer Hospital, Shanghai Medical University, Shanghai 200032, P.R. China.
Abstract:
The cyclin-dependent kinase inhibitor p16INK4a encoded by the INK4A/CDKN2A/MTS1 gene is a frequent target of 9p21 inactivation in human lung cancers. The p14ARF transcript, which is an alternative spliced form of this locus, is also altered or deleted in a proportion of human lung cancers and has been shown to inhibit cell cycle progression as an endogenous cellular regulator of the p53 protein, raising the possibility that it might constitute an additional lung tumor suppressor gene at the 9p21 locus. To test the candidacy of p14ARF as a lung cancer suppressor and assess the role it plays in radiosensitivity, we transfected the wild-type p14ARF gene into four cell lines which had various endogenous gene backgrounds of INK4A-/p53+/RB+ (A549 and H460), INK4A+/p53+/RB- (H446) as well as p14ARF+/p53-/RB+ (Calu-1). We found that transfection of p14ARF is related to an obvious growth inhibition in all wtp53 cell lines, regardless of INK4A/ARF and RB status. Although it has been shown that p53-induced G1 checkpoint in response to DNA damage by ionizing radiation is p14ARF-independent, we found the radiosensitivity of two p14ARF-deficient cell lines was increased after p14ARF gene transfer. The results indicated that cell cycle redistribution after acquiring the exogenous gene might be the main explanation for the enhanced sensitization. An increased radiation-induced apoptotic proportion in one cell line also suggested a fortified p53 function that might be triggered by the restored p14ARF protein.
Insights
The p14ARF gene, a potential lung cancer suppressor, inhibits tumor growth and enhances radiosensitivity in lung cancer cells. Restoring p14ARF function may fortify p53 activity, increasing treatment effectiveness.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- The INK4A/CDKN2A/MTS1 gene locus at 9p21 is frequently inactivated in lung cancers, targeting the p16INK4a protein.
- The p14ARF transcript, an alternative splice form of this locus, also shows alterations in lung cancers and regulates p53, suggesting a tumor suppressor role.
Purpose of the Study:
- To investigate the candidacy of p14ARF as a lung cancer suppressor gene.
- To evaluate the impact of p14ARF on the radiosensitivity of lung cancer cells.
Main Methods:
- Wild-type p14ARF gene transfection into four lung cancer cell lines with varying genetic backgrounds (INK4A, p53, RB status).
- Assessment of cell growth inhibition, cell cycle redistribution, and radiosensitivity post-transfection.
- Analysis of radiation-induced apoptosis and p53 function.
Main Results:
- p14ARF transfection induced significant growth inhibition in all wild-type p53 cell lines, irrespective of INK4A/ARF and RB status.
- Radiosensitivity increased in p14ARF-deficient cell lines following p14ARF gene transfer, potentially due to cell cycle redistribution.
- Enhanced radiation-induced apoptosis was observed in one cell line, suggesting a fortified p53 function.
Conclusions:
- p14ARF acts as a lung cancer suppressor gene, inhibiting cell proliferation.
- Restoration of p14ARF enhances lung cancer cell radiosensitivity, possibly through cell cycle modulation and p53 pathway activation.
- p14ARF may represent a therapeutic target for improving lung cancer treatment efficacy.
More Related Videos
Related Concept Videos
Abnormal Proliferation
Other Unique Bacteria

