Breast cancer is the most common malignancy affecting women’s health, with an increasing incidence worldwide. This study aimed to measure the intracellular concentration of the hypoxia-inducible factor 1 α (HIF-1α), tumor suppression protein p53, and estradiol (E2) in tumor tissues of adult females with breast cancer and their relation to tumor grade, tumor size, and lymph node metastases (LNM). The study was conducted on 65 adult female participants with breast mass admitted to the operating theater in Al-Hussein Teaching Hospital and Al-Habboby Teaching Hospital in Nasiriyah, Iraq, from January to November 2021. Fresh breast tumor tissues were collated and homogenized for intracellular biochemical analysis using the enzyme-linked immunosorbent assay method. In total, 44 (58%) out of 65 patients, in the age range of 18-42 years and the mean±SD age of 32.55±6.40 years, had fibroadenomas, and other 21 (42%) cases, in the age range of 32-80 years and the mean±SD age of 56±14.4 years had invasive ductal carcinoma (IDC) breast cancer. Intracellular levels of HIF-1α, p53, and E2 were elevated significantly (P<0.001) in IDC cases compared to the benign group. The most malignant tumors of IDC cases were in grade III and sizes T2 and T3. The tissue concentrations of HIF-1α, P53, and E2 were significantly elevated in patients with tumor stage T3 compared to T2 and T1. A significant elevation was found in the levels of HIF-1α, p53, and E2 in the positive LNM subgroup compared to the negative LNM group. Based on the obtained results, the prognostic value of the intracellular HIF-1α is considered to be a useful prognostic factor in Iraqi women with ICD and the combination of a HIF-1α protein with the nonfunctional p53 and E2 tends to indicate the proliferation, invasiveness, and metastases of the breast tumors. |
- Coad J, Pedley K, Dunstall M. Anatomy and physiology for midwives e-book: Elsevier Health Sciences; 2019.
- Ginsburg O, Yip CH, Brooks A, Cabanes A, Caleffi M, Dunstan Yataco JA, et al. Breast cancer early detection: A phased approach to implementation. Cancer. 2020;126:2379-93.
- Cummins EP, Strowitzki MJ, Taylor CT. Mechanisms and consequences of oxygen and carbon dioxide sensing in mammals. Physiol Rev. 2020;100(1):463-88.
- Zhou H, Guo M, Li J, Qin F, Wang Y, Liu T, et al. Hypoxia-triggered self-assembly of ultrasmall iron oxide nanoparticles to amplify the imaging signal of a tumor. J Am Chem Soc. 2021;143(4):1846-53.
- Al-Ostoot FH, Salah S, Khamees HA, Khanum SA. Tumor angiogenesis: Current challenges and therapeutic opportunities. Cancer Treat Res Commun. 2021;28:100422.
- Kewley RJ, Whitelaw ML, Chapman-Smith A. The mammalian basic helix–loop–helix/PAS family of transcriptional regulators. Int J Biochem Cell Biol. 2004;36(2):189-204.
- Lee S-H, Golinska M, Griffiths JR. HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells. Cells. 2021;10(9):2371.
- Feroz W, Sheikh AMA. Exploring the multiple roles of guardian of the genome: P53. Egypt J Med Hum Genet. 2020;21(1):1-23.
- Alvarado-Ortiz E, de la Cruz-López KG, Becerril-Rico J, Sarabia-Sánchez MA, Ortiz-Sánchez E, García-Carrancá A. Mutant p53 gain-of-function: role in cancer development, progression, and therapeutic approaches. Front Cell Dev Biol. 2021;8:1868.
- Maiti S, Nazmeen A. Impaired redox regulation of estrogen metabolizing proteins is important determinant of human breast cancers. Cancer Cell Int. 2019;19(1):1-13.
- Yager JD, Davidson NE. Estrogen carcinogenesis in breast cancer. N Engl J Med. 2006;354(3):270-82.
- Cavalieri E, Chakravarti D, Guttenplan J, Hart E, Ingle J, Jankowiak R, et al. Catechol estrogen quinones as initiators of breast and other human cancers: implications for biomarkers of susceptibility and cancer prevention. Biochim Biophys Acta-Rev Cancer. 2006;1766(1):63-78.
- Kido H. Portable Systems for Sample Lysis and Homogenization. Sample Preparation Techniques for Soil, Plant, and Animal Samples: Springer; 2016. p. 117-23.
- Mosher RA, Coetzee JF, Allen PS, Havel JA, Griffith GR, Wang C. Effects of sample handling methods on substance P concentrations and immunoreactivity in bovine blood samples. Am J Vet Res. 2014;75(2):109-16.
- Heikal L, Ghezzi P, Mengozzi M, Ferns G. Assessment of HIF-1α expression and release following endothelial injury in-vitro and in-vivo. Mol Med. 2018;24(1):1-10.
- John B, Henry J. Clinical diagnosis and management by laboratory methods. Clin Chem. 2001;20(4):570-5.
- Liu J, Zhang C, Zhao Y, Yue X, Wu H, Huang S, et al. Parkin targets HIF-1α for ubiquitination and degradation to inhibit breast tumor progression. Nat Commun. 2017;8(1):1-16.
- Corrado C, Fontana S. Hypoxia and HIF signaling: One axis with divergent effects. Int J Mol Sci. 2020;21(16):5611.
- Yang Y-S, Choi JH, Rah J-C. Hypoxia with inflammation and reperfusion alters membrane resistance by dynamically regulating voltage-gated potassium channels in hippocampal CA1 neurons. Mol Brain. 2021;14(1):1-12.
- Malkov MI, Lee CT, Taylor CT. Regulation of the Hypoxia-Inducible Factor (HIF) by Pro-Inflammatory Cytokines. Cells. 2021;10(9):2340.
- Emami Nejad A, Najafgholian S, Rostami A, Sistani A, Shojaeifar S, Esparvarinha M, et al. The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment. Cancer Cell Int. 2021;21(1):1-26.
- Liu Z-j, Semenza GL, Zhang H-f. Hypoxia-inducible factor 1 and breast cancer metastasis. J Zhejiang Univ Sci B. 2015;16(1):32-43.
- Cimmino F, Avitabile M, Lasorsa VA, Montella A, Pezone L, Cantalupo S, et al. HIF-1 transcription activity: HIF1A driven response in normoxia and in hypoxia. BMC Med Gen. 2019;20(1):1-15.
- Vaupel P, Schlenger K, Knoop C, Höckel M. Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements. Cancer Res. 1991;51(12):3316-22.
- Bourdon J-C. p53 and its isoforms in cancer. Br J Cancer. 2007;97(3):277-82.
- Bellazzo A, Sicari D, Valentino E, Del Sal G, Collavin L. Complexes formed by mutant p53 and their roles in breast cancer. Breast Cancer 2018;10:101.
- Labuschagne CF, Zani F, Vousden KH. Control of metabolism by p53–cancer and beyond. Biochim Biophys Acta-Rev. Cancer. 2018;1870(1):32-42.
- Shi Y, Norberg E, Vakifahmetoglu-Norberg H. Mutant p53 as a regulator and target of autophagy. Front Oncol. 2021:3300.
- Estevão RAF, Nazário ACP, Baracat EC. Effect of oral contraceptive with and without associated estriol on ultrasound measurements of breast fibroadenoma: randomized clinical trial. Sao Paulo Med J. 2007;125(5):275-80.
- Russo J, Russo IH. The role of estrogen in the initiation of breast cancer. J Steroid Biochem Mol Biol. 2006;102(1-5):89-96.
- Kulendran M, Salhab M, Mokbel K. Oestrogen-synthesising enzymes and breast cancer. Anticancer Res. 2009;29(4):1095-109.
- Zhang C, Liu J, Wang J, Zhang T, Xu D, Hu W, et al. The interplay between tumor suppressor p53 and hypoxia signaling pathways in cancer. Front Cell Dev Biol. 2021;9:273.
- Madan E, Parker TM, Pelham CJ, Palma AM, Peixoto ML, Nagane M, et al. HIF-transcribed p53 chaperones HIF-1α. Nucleic Acids Res. 2019;47(19):10212-34.
- Opoku F, Bedu-Addo K, Titiloye NA, Atta Manu E, Ameh-Mensah C, Duduyemi BM. Expression profile of tumour suppressor protein p53 and its regulator MDM2 in a cohort of breast cancer patients in a Tertiary Hospital in Ghana. Plos One. 2021;16(10):0258543.
- Yang J, Harris AL, Davidoff AM. Hypoxia and hormone-mediated pathways converge at the histone demethylase KDM4B in cancer. Int J Mol Sci. 2018;19(1):240.
- Karataşlı V, Erkılınç S, Çakır İ, Can B, Karadeniz T, Gökçü M, et al. The effect of lymph node metastasis on overall survival and disease-free survival in vulvar cancer patients. Ginekol Pol. 2020;91(2):62-7.
|