Mutations of genes responsible for the growth and division of cells in adenocarcinoma and squamous cell lung cancer
https://doi.org/10.24412/2790-1289-2023-4-10-19
Abstract
P53 (encoding the p53 protein) is one of the most frequently mutated genes in all human cancer diseases. Common missense mutations of p53 abolish its tumor-suppressing function (gain-of-function, GOF)
and lead to the development of GOF cancer.
Materials and Methods. The study focused on samples of squamous cell carcinoma, adenocarcinoma of the lungs, and adjacent healthy tissues obtained from postoperative material of cancer patients.
Methods included polymerase chain reaction of p53 and HRAS gene fragments, as well as complementary DNA (c-DNA) copies of p53, p21Waf1, MDM2, and mutation analysis using EcoR1 and Pst1 endonucleases based on restriction site presence.
Results. The presence of mutations was analyzed after amplification of p53 and HRAS gene fragments, as well as p53, p21Waf1, and MDM2 mRNA in cancerous and adjacent tissues in 100 samples of tumor and normal adjacent tissues. Half of the SCC and ADC lung samples did not contain expression products of p53 or p21Waf1 genes. Mutations were detected in 100 % and 85 % of SCC samples in 12 and
61 codons of the HRAS gene, and in 75 % and 50 % of ADC samples, respectively.
Conclusion. Mutations found in the majority of SCC and ADC samples allow diagnosing the disease, predicting its severity, and assessing the effectiveness of targeted therapy through such tests.
About the Authors
S. A. YermekovaKazakhstan
Ermekova Saule Alikhanovna, Doctor of Medical Sciences, Professor,
Almaty.
B. T. Zhanataev
Kazakhstan
Zhanataev Bauyrzhan Turalyuly, Master's degree, Senior Lecturer,
Almaty.
E. S. Serik
Kazakhstan
Serik Elmire Serikkazy, Master of Pedagogical Sciences, Senior Lecturer,
Almaty.
References
1. Zhu, J., Sammons, M. A., Donahue, G., Dou, Z., Vedadi, M., Getlik, M., Barsyte-Lovejoy, D., Al-war, R., Katona, B. W., Shilatifard, A., Huang, J., Hua, X., Arrowsmith, C. H. and Berger, S. L. (2015). Gain-of-function p53 mutants coopt chromatin pathways to drive cancer growth. Nature, 525(7568), 206-211, DOI: 10.15252/embj.201899599.
2. Ding, J., Yu, C., Sui, Y., Wang, L., Yang, Y., Wang, F., Yao, H., Xing, F., Liu, H., Li, Y., Shah, J. A., Cai, Y. and Jin, J. (2018). The chromatin remodeling protein INO80 contributes to the removal of H2A.Z at the p53‐binding site of the p21 gene in response to doxorubicin. The FEBS Journal, 285, 3270-3285, DOI: 10.1111/febs.14615.
3. Sui, Y., Wu, T., Li, F., Wang, F., Cai, Y. and Jin, J. (2019). YY1 / BCCIP Coordinately Regulates P53Responsive Element (p53RE)-Mediated Transactivation of p21 Waf1 / Cip1. International Journal of Molecular Sciences, 20(9), 2095, DOI: 10.3390/ijms20092095.
4. Meliala, ITS., Hosea, R., Kasim, V. and Wu, S. (2020). The biological implications of Yin Yang 1 in the hallmarks of cancer. Theranostics, 10(9), 4183-4200, DOI: 10.7150/thno.43481.
5. Cao, L., Ding, J., Dong, L., Zhao, J., Su, J., Wang, L., Sui, Y., Zhao, T., Wang, F. and Jin, J. (2015). Negative Regulation of p21Waf1/Cip1 by Human INO80 Chromatin Remodeling Complex Is Implicated in Cell Cycle Phase G2/M Arrest and Abnormal Chromosome Stability. PLoS ONE, 10(9), 0137411, DOI: 10.1371/journal.pone.0137411.
6. Khoury, K. and Domlng, A. P53 Mdm2 Inhibitors. Current Pharmaceutical Design, 2012, 18(30), 4668-4678, DOI: 10.2174/138161212802651580/.
7. Estrada-Ortiz, N., Neochoritis, C. G. and Domling, A. (2016). How to Design a Successful p53MDM2/X Interaction Inhibitor: A Thorough Overview Based on Crystal Structures. ChemMedChem, 11(8), 757-772, DOI: 10.1002/cmdc.201500487.
8. To, M. D., Rosario, R. D., Westcott, P. M., Banta, K. L. and Balmain, A. (2013). Interactions between wild-type and mutant Ras genes in lung and skin carcinogenesis. Oncogene, 32(34), 4028-4033, DOI: 10.1038/onc.2012.404.
9. Asfar, S. (2016). Conquering RAS, 1st ed. Academic Press, 297 p.
10. Mehta, A., Dalle Vedove, E., Isert, L. and Merkel, O. M. (2019). Targeting KRAS Mutant Lung Cancer Cells with siRNA-Loaded Bovine Serum Albumin Nanoparticles. Pharmaceutical Research, 36(9), 133, DOI: 10.1007/s11095-0192665-9.
11. Naghizadeh, S., Mohammadi, A., Baradaran, B. and Mansoori, B. (2019). Overcoming multiple drug resistance in lung cancer using siRNA targeted therapy. Gene, 714, 143972, DOI: 10.1016/j.gene.2019.143972.
12. Singh, S. S., Dahal, A., Shrestha, L. and Jois, S. D. (2020). Genotype driven therapy for non-small cell lung cancer: resistance, pan inhibitors and immunotherapy. Current Medical Chemistry, 27, 5274, DOI: 10.2174/0929867326666190222183219.
13. Hay, N. and Sonenberg, N. (2004). Upstream and downstream of mTOR. Genes & Development, 18, 1926-1945, DOI: 10.1101/gad.1212704.
14. Beevers, C. S., Li, F., Liu, L. and Huang, S. (2006). Curcumin inhibits the mammalian target of rapamycin-mediated signaling pathways in cancer cells. International Journal of Cancer, 119, 757764, DOI: 10.1002/ijc.21932.
15. Liu, X., Zhang, X., Meng, J., Zhang, H., Zhao, Y., Li, C., Sun, Y., Mei, Q., Zhang, F. and Zhang, T. (2017). ING5 knockdown enhances migration and invasion of lung cancer cells by inducing EMT via EGFR/PI3K/Akt and IL-6/STAT3 signaling pathways. Oncotarget, 8, 54265-54276, DOI: 10.18632/oncotarget.17346.
16. Kawano, O., Sasaki, H., Endo, K., Suzuki, E., Haneda, H., Yukiue, H., Kobayashi, Y., Yano, M. and Fujii, Y. (2006). PIK3CA mutation status in Japanese lung cancer patients. Lung Cancer, 54, 209-215, DOI: 10.1016/j.lungcan.2006.07.006.
Review
For citations:
Yermekova S.A., Zhanataev B.T., Serik E.S. Mutations of genes responsible for the growth and division of cells in adenocarcinoma and squamous cell lung cancer. Actual Problems of Theoretical and Clinical Medicine. 2023;(4):10-19. (In Russ.) https://doi.org/10.24412/2790-1289-2023-4-10-19