Marwa Mohammed Ali Jassim, Shaymaa A. Naji, Majid Mohammed Mahmood
Marwa Mohammed Ali Jassim1, Shaymaa A. Naji2, Majid Mohammed Mahmood3
1College of Dentistry, Al-Muthanna University, Al-Muthanna, Iraq.
2Dep. of Medical Laboratory Techniques, Al- Nisour University College, Baghdad, Iraq.
3Dep. of Biology, College of Science, Mustansiriyah University, Baghdad, Iraq.
Volume - 15,
Issue - 9,
Year - 2022
The retinoblastoma (RB) gene encodes the retinoblastoma pocket protein, which controls the cell cycle by binding to unphosphorylated E2F transcription factors and inhibiting their activation. The function of BRCA1 and the anti-apoptotic protein Bcl-2 in lung cancer, however, is still debated. Objective:The purpose of this research is to look at the relationship between the cell-cycle proteins BRCA1, BCL2, and RB and lung cancer etiology and progression. Experimental Design: Cases from major hospitals and many private histopathological laboratories between 2018 and 2021 were reviewed for immunohistochemical expression of BRCA1, BCL2, and RB. A total of 60 people (20 healthy people as a control group and 40 patients with lung carcinoma) were reviewed and analyzed for immunohistochemical expression of these genes. Results: In (90.0%) of cases, RB-IHC was overexpressed, according to the data. The BRCA1 overexpression was seen in (95.0 %). Though BCL2 was overexpressed in (92.5%) of the cases. When comparing the healthy and lung cancer groups, there is a highly significant difference at (P<0.01). Conclusion: Overexpression of RB, BRCA1, and BCL2 in lung cancers with little or no regulatory role may suggest mutational events, which act in collaboration with numerous other genetic mutations in these tissues. The study findings indicate that disruption of cell cycle proteins may perform a unique function in lung cancer disease onset and development and suggest that all patients have abnormalities in the BRCA1, BCL2, and RB proteins. have a role in lung carcinomas.
Cite this article:
Marwa Mohammed Ali Jassim, Shaymaa A. Naji, Majid Mohammed Mahmood. BRCA1, BCL2, and the RB Tumor Suppressor have abnormal expressions in lung cancer. Research Journal of Pharmacy and Technology. 2022; 15(9):4083-7. doi: 10.52711/0974-360X.2022.00685
Marwa Mohammed Ali Jassim, Shaymaa A. Naji, Majid Mohammed Mahmood. BRCA1, BCL2, and the RB Tumor Suppressor have abnormal expressions in lung cancer. Research Journal of Pharmacy and Technology. 2022; 15(9):4083-7. doi: 10.52711/0974-360X.2022.00685 Available on: https://rjptonline.org/AbstractView.aspx?PID=2022-15-9-45
1. Mynard N. Saxena A. Mavracick A. Port J. et al.. Lung Cancer Stage Shift as a Result of COVID-19 Lockdowns in New York City, a Brief Report. Clinical Lung Cancer. 2021; 29: S1525-7304 (21) 00214-X. doi: 10.1016/j.cllc.2021.08.010.
2. Zappa C. Mousa SA. Non-small cell lung cancer: current treatment and future advances. Translational lung cancer research. 2016; 5(3): 288-300. doi:10.21037/tlcr.2016.06.07
3. Saad H. Mohammed A. Taghreed F. Almahbobi Y. et al. Impact of Human Cytomegalovirus Infection associated with the expressed protein of mutated BRCA1 gene in breast tissues from a group of Iraqi Female Patients with Breast Carcinoma. Research Journal of Pharmacy and Technology. 2018; 11(4): 1505-1512. doi:10.5958/0974-360X.2018.00280.9
4. Cruz CSD. Tanoue LT. Matthay RA. Lung cancer: epidemiology, etiology, and prevention. Clinics in chest medicine. 2011; 32(4): 605-644. doi: 10.1016/j.ccm.2011.09.001
5. Fares J. Fares MY. Khachfe HH. Salhab HA. Fares Y. Molecular principles of metastasis: a hallmark of cancer revisited. Signal transduction and targeted therapy. 2020; 5(1): 1-17. doi.org/10.1038/s41392-020-0134-x
6. Francis AM. Ramya R. Ganesan N. Kumarasamy P. et al. Analysis of BRCA1 gene exon 2 mutation in breast cancer patients in a South Indian population . Research Journal of Pharmacy and Technology. 2018; 11(10): 4592-4596. DOI:10.5958/0974-360X.2018.00840.5
7. Andreassen PR. Seo J. Wiek C. Hanenberg H. Understanding BRCA2 Function as a Tumor Suppressor Based on Domain-Specific Activities in DNA Damage Responses. Genes. 2021; 12(7): 1034. doi:10.3390/genes12071034.
8. Lee YC. Lee YC. Li CY. Lee YL. Chen BL. BRCA1 and BRCA2 gene mutations and lung cancer risk: a meta-analysis. Medicina. 2020; 56(5): 212. doi:10.3390/medicina56050212
9. Maccaroni E. Giampieri R. Lenci E. Scortichini L. et al. BRCA mutations and gastrointestinal cancers: When to expect the unexpected?. World Journal of Clinical Oncology. 2021; 12(7), 565. doi: 10.5306/wjco.v12.i7.565.
10. Fehm TN. Stickeler E. Fasching PA. Janni W. et al. Update Breast Cancer 2021 Part 3–Current Developments in the Treatment of Early Breast Cancer: Review and Assessment of Specialised Treatment Scenarios by an International Expert Panel. Geburtshilfe und Frauenheilkunde. 2021; 81(06): 654-665. doi:10.1055/a-1487-7642
11. Rabkin CS. Hirt C. Janz S. Dölken G. t (14; 18) Translocations and risk of follicular lymphoma. Journal of the National Cancer Institute Monographs. 2008; 2008(39): 48-51. doi: 10.1093/jncimonographs/lgn002
12. Reddy YVK. Reddy PS. Shivalinga MR. Protective Effects of Testosterone on Cisplatin Induced Impairment of Spermatogenesis and Steroidogenesis in Rats. Research Journal of Pharmacy and Technology. 2010; 3(2): 535-539.
13. Colombel M. Symmans F. Gil S. O'toole KM. et al. Detection of the apoptosis-suppressing oncoprotein bc1-2 in hormone-refractory human prostate cancers. The American journal of pathology. 1993; 143(2): 390.
14. Silvestrini R. Veneroni S. Daidone MG. Benini E. et al. The Bcl-2 protein: a prognostic indicator strongly related to p53 protein in lymph node-negative breast cancer patients. JNCI: Journal of the National Cancer Institute, 1994; 86(7): 499-504.
15. Fontanini G. Vignati S. Bigini D. Mussi A. et al. Recurrence and death in non-small cell lung carcinomas: a prognostic model using pathological parameters, microvessel count, and gene protein products. Clinical cancer research. 1996; 2(6): 1067-1075.
16. Rachmi E. Purnomo BB. Endharti AT. Fitri LE. In silico prediction of Anti-apoptotic BCL-2 proteins Modulation by Afzelin in MDA-MB-231 Breast cancer cell. Research Journal of Pharmacy and Technology. 2020; 13(2):905-910. DOI:10.5958/0974-360X.2020.00171.7
17. Gross A. Katz SG. Non-apoptotic functions of BCL-2 family proteins. Cell Death & Differentiation. 2017; 24(8): 1348-1358. doi: 10.1038/cdd.2017.22.
18. Soebagjo HD. Fatmariyanti S. Sugianto P. Purwanto B. et al. Detection of the Calcium and ATP Role in Apoptosis of Retinoblastoma Culture Cells through Caspase-3 Expression. 12(3):1307. DOI:10.5958/0974-360X.2019.00219.1
19. Mandigo AC. Yuan W. Xu K. Gallagher P. et al. RB/E2F1 as a master regulator of cancer cell metabolism in advanced disease. Cancer Discovery. 2021; 11(9):2334-2353. doi: 10.1158/2159-8290.CD-20-1114.
20. Hendrian D. Fatmariyanti SS. Sugianto P. Purwanto B. et al. Detection of the Calcium and ATP Role in Apoptosis of Retinoblastoma Culture Cells through Caspase-3 Expression. Research Journal of Pharmacy and Technology. 2019; 12(3): 1307. DOI:10.5958/0974-360X.2019.00219.1
21. Chen L. Liu S. Tao Y. Regulating tumor suppressor genes: post-translational modifications. Signal Transduction and Targeted Therapy. 2020; 5(1): 90. doi:10.1038/s41392-020-0196-9
22. Verdugo-Sivianes EM. Carnero A. Role of the Holoenzyme PP1-SPN in the Dephosphorylation of the RB Family of Tumor Suppressors During Cell Cycle. Cancers. 2021; 13(9): 2226. doi: 10.3390/cancers13092226.
23. Hussein AA. Khashman BM. Hussain SM. Role of Tgf-b1and Gremlin-1 in the Pathogenesis of Chronic HCV Infection and Hepatocellular Carcinoma. Inhdian Journal of Applied Research. 2013; 3(9): 75-78. DOI:10.15373/2249555X/SEPT2013/148
24. Hagawane TN. Mahuvakar AM. Gaikwad RV. Kshirsagar NA. Intratracheal (IT) Lipopolysaccharide (LPS) Induced Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS) in Wistar Rats. Research Journal of Pharmacy and Technology. 2014; 7(4): 419-426.
25. Higashiyama M., Doi O. Kodama K. Yokouchi H. Tateishi R. Retinoblastoma protein expression in lung cancer: an immunohistochemical analysis. Oncology. 1994; 51(6): 544-551.
26. Dosaka‐Akita H. Hu SX. Fujino M. Harada M. et al. Altered retinoblastoma protein expression in nonsmall cell lung cancer: its synergistic effects with altered ras and p53 protein status on prognosis. Cancer: Interdisciplinary International Journal of the American Cancer Society, 1997; 79(7): 1329-1337.
27. Xu HJ. Cagle PT. Hu SX. Li J. Benedict WF. Altered retinoblastoma and p53 protein status in non-small cell carcinoma of the lung: potential synergistic effects on prognosis. Clinical cancer research. 1996; 2(7): 1169-1176.
28. Nishio M. Koshikawa T. Yatabe Y. Kuroishi T. et al. Prognostic significance of cyclin D1 and retinoblastoma expression in combination with p53 abnormalities in primary, resected non-small cell lung cancers. Clinical cancer research. 1997; 3(7): 1051-1058.
29. Dosaka‐Akita H. Cagle PT. Hiroumi H. Fujita M. et al. Differential retinoblastoma and p16INK4A protein expression in neuroendocrine tumors of the lung. Cancer. 2000; 88(3): 550-556.
30. Linn P. Kohno S. Sheng J. Kulathunga N. et al. Targeting RB1 Loss in Cancers. Cancers. 2021; 13(15): 3737. https://doi.org/10.3390/cancers13153737
31. Hagawane EN. Mahuvakar AM. Gaikwad RV. Kshirsagar NA. Oleic Acid Induced Acute Lung Injury/Acute Respiratory Distress Syndrome Animal Model. Research Journal of Pharmay and Technology. 2014; 7(8): 882-888.
32. Linn P. Kohno S. Sheng J. Kulathunga N. et al. Targeting RB1 Loss in Cancers. Cancers. 2021; 13(15): 3737.
33. Hussein HH, Alsabari EK. Kadhim BA. Hatif KH. et al. Study the Impact of the Trace Elements between the Healthy Females and who take Chemotherapy for samples of Sera. Research Journal of Pharmacy and Technology. 2017; 10(10): 3323-3325. DOI:10.5958/0974-360X.2017.00589.3
34. Leonetti, A. Minari R. Mazzaschi G. Gnetti L. et al. Small Cell Lung Cancer Transformation as a Resistance Mechanism to Osimertinib in Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma: Case Report and Literature Review. Frontiers in Oncology. 2021; 11: 642190. doi:10.3389/fonc.2021.642190
35. Gachechiladze M. Skarda J. The role of BRCA1 in non-small cell lung cancer. Biomedical Papers. 2012; 156(3): 200-203.
36. Padmini R. Sitrarasi R. Razia M. Molecular Docking Studies of Bioactive Compounds from Allium sativum Against EML4-ALK Receptor. Research Journal of Pharmacy and Technology. 2017; 10(11): 3741-3747. DOI:10.5958/0974-360X.2017.00679.5
37. Lee YC. Lee YC. Li CY. Lee YL. Chen BL. BRCA1 and BRCA2 gene mutations and lung cancer risk: a meta-analysis. Medicina. 2020; 56(5): 212. doi:10.3390/medicina56050212
38. Fiorentino M. Judson G. Penney K. Flavin R. et al. Immunohistochemical expression of BRCA1 and lethal prostate cancer. Cancer Research. 2010; 70(8): 3136-3139.
39. Lewis DR. Check DP. Caporaso NE. Travis WD. Devesa SS. US lung cancer trends by histologic type. Cancer. 2014; 120(18): 2883-2892. doi: 10.1002/cncr.28749.
40. AACR Project Genie Consortium. AACR Project GENIE: powering precision medicine through an international consortium. Cancer Discovery. 2017; 7(8), 818-831.
41. Zhang J. Wang S. Wang L. Wang R. et al. Prognostic value of Bcl-2 expression in patients with non-small-cell lung cancer: A meta-analysis and systemic review. OncoTargets and Therapy. 2015; 2015(8): 3361-3369. doi:10.2147/OTT.S89275.
42. Singh K. Briggs JM. Functional Implications of the spectrum of BCL2 mutations in Lymphoma. Mutation Research/Reviews in Mutation Research. 2016; 769: 1-18. doi: 10.1016/j.mrrev.2016.06.001.
43. Tas F. Duranyildiz D. Oguz H. Camlica H. et al. The value of serum Bcl-2 levels in advanced lung cancer patients. Medical Oncology. 2005; 22(2): 139-143). doi: 10.1385/MO:22:2:139.