The Correlation between P53 and Interleukins (IL-2, IL-8) and their role in Breast Cancers P53 and Interleukins (IL-2, IL-8) role in Breast Cancers

Mayada Al-khafaji (1), Zaedoon Monaam (2), Elham Majeed Flayh (3)
(1) Department of Medical lab. Techniques, College of Health and Medical Techniques, Gilgamesh University, Baghdad, Iraq., Iraq,
(2) Department of Medical lab. Techniques, College of Health and Medical Techniques, Gilgamesh University, Baghdad, Iraq., Iraq,
(3) Al-Iraqia Uiversity, Baghdad, Iraq, Iraq

Abstract

Abstract
Background: The p53 gene, a tumor suppressor and the custodian of the genome, is essential for preserving genomic stability in the nucleus of every cell. This research aimed to study the correlation between Interleukins and p53, in addition to investigate the potential link between p53 and the development of cancerous lesions, particularly in breast cancer.
Methods: Sixty blood samples were collected from 40 breast cancer patients at Medical City Hospital/ Baghdad, while 20 control healthy individuals from a volunteer students at the Gilgamesh University. Quantitative real-time polymerase chain reaction (RT-PCR) was done to assess the expression levels of the p53 gene. Whereas, ELISA was used to determine the levels of (IL-2,IL-8 and P53 titer).
Results: The mean and standard deviation of the levels of IL-2 and IL-8 were 10.6± 3.2 pg/ml and 25.7± 4.5pg/ml) respectively for breast cancer patients , in compare with control (2.8± 1.9pg/ml, 8.3± 1.0 pg/ml), respectivel. However, the expression of P53 was decreased in patients (129.7 ± 55.9 pg/ml) compared to control. Additional, 11 of the 15 breast cancer samples used for RT-PCR exhibited significantly lower p53 expression. These findings suggest a potential correlation between downregulation of p53 expression and breast cancer development. The results showed a significant difference in p53 expression between controls and patients (P > 0.05).
In conclusion, the results showed increasing IL-2 and IL-8 and decreasing p53 levels, in breast cancer patients . Consequently, this study approved that IL-2 and IL-8 are important biomarkers for prognosis and diagnosis and have a significant influence on the development of breast cancer.

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References

Smolarz B, Nowak AZ, Romanowicz H. Breast Cancer—Epidemiology, Classification, Pathogenesis and Treatment (Review of Literature). Cancers (Basel). 2022;14(10):2569. doi:10.3390/cancers14102569

Fasoulakis Z, Kolios G, Papamanolis V, Kontomanolis EN. Interleukins Associated with Breast Cancer. Cureus. Published online November 5, 2018. doi:10.7759/cureus.3549

Todorović-Raković N, Milovanović J. Interleukin-8 in Breast Cancer Progression. Journal of Interferon & Cytokine Research. 2013;33(10):563-570. doi:10.1089/jir.2013.0023

Al-Hasso IK. Assessment of Serum Soluble Toll-like Receptor-4 and Interleukin-8 as Biomarkers in Patients with Breast Cancer. Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 ). 2024;6(1):167-171. doi:10.54133/ajms.v6i1.568

Levine AJ. P53 and The Immune Response: 40 Years of Exploration—A Plan for the Future. Int J Mol Sci. 2020;21(2):541. doi:10.3390/ijms21020541

Karima Al Salihi, Ihsan Abdullah, S. L. Ang. Histological implication of p53 gene expression in oral squamous cell carcinoma. Journal of cellular cancer. 2016;8(1):60-69.

Hafner A, Bulyk ML, Jambhekar A, Lahav G. The multiple mechanisms that regulate p53 activity and cell fate. Nat Rev Mol Cell Biol. 2019;20(4):199-210. doi:10.1038/s41580-019-0110-x

Timofeev O. Editorial: Mutant p53 in Cancer Progression and Personalized Therapeutic Treatments. Front Oncol. 2021;11. doi:10.3389/fonc.2021.740578

Levine AJ. The many faces of p53: something for everyone. J Mol Cell Biol. 2019;11(7):524-530. doi:10.1093/jmcb/mjz026

Harris SL, Levine AJ. The p53 pathway: positive and negative feedback loops. Oncogene. 2005;24(17):2899-2908. doi:10.1038/sj.onc.1208615

Marei HE, Althani A, Afifi N, et al. p53 signaling in cancer progression and therapy. Cancer Cell Int. 2021;21(1):703. doi:10.1186/s12935-021-02396-8

Karima Akool Al-Salihi, S. L. Ang, A. Azlina, M.S. Farini, H. Jaffar. Immunohistochemical and molecular genetic analysis of p 53 in oral squamous cell carcinoma (scc) in Hospital University Science Malaysia: a preliminary study. Braz J Oral Sci. 2008;7(24).

Levine AJ. Spontaneous and inherited TP53 genetic alterations. Oncogene. 2021;40(41):5975-5983. doi:10.1038/s41388-021-01991-3

Philomena George. P53 HOW CRUCIAL IS ITS ROLE IN CANCER? International Journal of Current Pharmaceutical Research . 2011;3(2).

Al-Saady RK. The Impact of Body Mass Index and Some Trace Elements in Iraqi Women with Breast Cancer. J Fac Med Baghdad. 2016;57(4):312-315. doi:10.32007/jfacmedbagdad.574397

Mauro L, Naimo GD, Gelsomino L, et al. Uncoupling effects of estrogen receptor α on LKB1/AMPK interaction upon adiponectin exposure in breast cancer. The FASEB Journal. 2018;32(8):4343-4355. doi:10.1096/fj.201701315R

Matthews S, Thompson H. The Obesity-Breast Cancer Conundrum: An Analysis of the Issues. Int J Mol Sci. 2016;17(6):989. doi:10.3390/ijms17060989

Khalil S, Hatch L, Price CR, et al. Addressing Breast Cancer Screening Disparities Among Uninsured and Insured Patients: A Student-Run Free Clinic Initiative. J Community Health. 2020;45(3):501-505. doi:10.1007/s10900-019-00767-x

Heer E, Harper A, Escandor N, Sung H, McCormack V, Fidler-Benaoudia MM. Global burden and trends in premenopausal and postmenopausal breast cancer: a population-based study. Lancet Glob Health. 2020;8(8):e1027-e1037. doi:10.1016/S2214-109X(20)30215-1

Johnson KC, Houseman EA, King JE, Christensen BC. Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age. Breast Cancer Research. 2017;19(1):81. doi:10.1186/s13058-017-0873-y

Wu C, Li M, Meng H, et al. Analysis of status and countermeasures of cancer incidence and mortality in China. Sci China Life Sci. 2019;62(5):640-647. doi:10.1007/s11427-018-9461-5

Portakal O, Özkaya Öz, Erden i̇nal M, Bozan B, Koşan M, Sayek I. Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clin Biochem. 2000;33(4):279-284. doi:10.1016/S0009-9120(00)00067-9

Al-Ghurabi BH. IL-2 and IL-4 Serum Levels in Breast Cancer. J Fac Med Baghdad. 2009;51(3):300-303. doi:10.32007/jfacmedbagdad.5131130

Essa S, Siddique I, Saad M, Raghupathy R. Modulation of Production of Th1/Th2 Cytokines in Peripheral Blood Mononuclear Cells and Neutrophils by Hepatitis C Virus Infection in Chronically Infected Patients. Pathogens. 2021;10(11):1519. doi:10.3390/pathogens10111519

Muraro E, Martorelli D, Turchet E, et al. A different immunologic profile characterizes patients with HER-2-overexpressing and HER-2-negative locally advanced breast cancer: implications for immune-based therapies. Breast Cancer Research. 2011;13(6):R117. doi:10.1186/bcr3060

WANG YC, WANG ZH, YEN JH, et al. The Contribution of Interleukin-8 Rs4073 Genotypes to Triple Negative Breast Cancer Risk in Taiwan. Anticancer Res. 2022;42(8):3799-3806. doi:10.21873/anticanres.15870

Al-Hasso IK. Assessment of Serum Soluble Toll-like Receptor-4 and Interleukin-8 as Biomarkers in Patients with Breast Cancer. Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 ). 2024;6(1):167-171. doi:10.54133/ajms.v6i1.568

Mohsin SAM, Al-Thwani AN. Clinical importance of interleukin-8 concentration in Iraqi breast cancer patients. . Iraqi J Biotechnol 2012;11(1):133-140. 2012;11(1):133-140.

MATSUI T, OJIMA A, HIGASHIMOTO Y, TAIRA J, FUKAMI K, YAMAGISHI SI. Pigment epithelium-derived factor inhibits caveolin-induced interleukin-8 gene expression and proliferation of human prostate cancer cells. Oncol Lett. 2015;10(4):2644-2648. doi:10.3892/ol.2015.3568

Ghazwan Sabah Kamel, Salih Mahdi Salman, Walaa Najim Abood. Evaluation of P53 and Some Blood Parameters In Women Diagnosed With Breast Cancer. Diyala Journal of Medicine . 2019;17(1).

Al-Hassan Ahmed AA. Detection of serum anti-p53 antibodies in breast cancer patients. Al-Mustansiriyah Journal of Science . Published online 2011:7-12.

Børresen-Dale AL. TP53 and breast cancer. Hum Mutat. 2003;21(3):292-300. doi:10.1002/humu.10174

Pützer BM, Bramson JL, Addison CL, et al. Combination Therapy with Interleukin-2 and Wild-Type p53 Expressed by Adenoviral Vectors Potentiates Tumor Regression in a Murine Model of Breast Cancer. Hum Gene Ther. 1998;9(5):707-718. doi:10.1089/hum.1998.9.5-707

Yuan A, Yu CJ, Luh KT, Kuo SH, Lee YC, Yang PC. Aberrant p53 Expression Correlates With Expression of Vascular Endothelial Growth Factor mRNA and Interleukin-8 mRNA and Neoangiogenesis in Non–Small-Cell Lung Cancer. Journal of Clinical Oncology. 2002;20(4):900-910. doi:10.1200/JCO.2002.20.4.900

Feroz W, Sheikh AMA. Exploring the multiple roles of guardian of the genome: P53. Egyptian Journal of Medical Human Genetics. 2020;21(1):49. doi:10.1186/s43042-020-00089-x

Schumacher B, Pothof J, Vijg J, Hoeijmakers JHJ. The central role of DNA damage in the ageing process. Nature. 2021;592(7856):695-703. doi:10.1038/s41586-021-03307-7

Engeland K. Cell cycle regulation: p53-p21-RB signaling. Cell Death Differ. 2022;29(5):946-960. doi:10.1038/s41418-022-00988-z

Gasco M, Shami S, Crook T. The p53 pathway in breast cancer. Breast Cancer Research. 2002;4(2):70. doi:10.1186/bcr426

Marei HE, Althani A, Afifi N, et al. p53 signaling in cancer progression and therapy. Cancer Cell Int. 2021;21(1):703. doi:10.1186/s12935-021-02396-8

D Kandioler-Eckersberger, C Ludwig, M Rudas, et al. TP53 mutation and p53 overexpression for prediction of response to neoadjuvant treatment in breast cancer patients. Clin Cancer Res . 2000;6(1):50-56.

Mohan A, Jindal B, Thakral RK, Ansari V, Sharma VK. Role of p53 as a prognostic marker in breast carcinoma and its correlation with tumor size, tumor grade and lymph node metastasis. Indian Journal of Pathology and Oncology. 2020;7(3):378-383. doi:10.18231/j.ijpo.2020.076

Authors

Mayada Al-khafaji
mayada.h.mahdi@gu.edu.iq (Primary Contact)
Zaedoon Monaam
Elham Majeed Flayh
1.
Al-khafaji M, Monaam Z, Flayh EM. The Correlation between P53 and Interleukins (IL-2, IL-8) and their role in Breast Cancers: P53 and Interleukins (IL-2, IL-8) role in Breast Cancers. Arch Breast Cancer [Internet]. [cited 2025 Jul. 17];12(2). Available from: https://archbreastcancer.com/test/index.php/abc/article/view/1071

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