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Correlation of expression of Akt1 and E2F1 and their phosphorylated forms in breast cancer patients with clinicopathological parameters

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Abstract

Breast cancer is the leading cancer worldwide among women. Traditional clinicopathological prognostic and predictive markers need refining to improve clinical outcomes. This study explored the association between traditional clinicopathological factors and the expression of Akt1 and E2F1 transduction proteins and their phosphorylated forms in breast cancer, to determine their value as novel biomarkers and potential therapeutic targets. Tumor tissues from 94 female breast cancer patients were examined for immunophenotypic expression of total Akt1, pAkt1 (Serine 473), pAkt1 (Threonine 308), total E2F1, pE2F1 (Thr433) and pE2F1 (Ser337). The expression of pAkt1 (Ser473) was significantly associated with ER/PR positive status and total E2F1 with older age (> 50), lymph node involvement and HER2 positivity. There was a significant association between triple negative cancers and total and pAkt1 (Thr308). pAkt1 (Ser473) showed an inverse relationship with Luminal B cancers and pE2F1 (Thr433) showed an inverse association with triple negative cancers. Higher expression of pE2F1 (Ser337) was associated with better OS. Both pAkt1 (Ser473 and Thr308) proteins showed significant association with poorer patient outcomes. E2F1 (Ser337) showed a significant positive correlation with response to chemotherapy. The study suggests that a pAkt1−/pE2F1+ phenotype could indicate an opportunity to minimize chemotherapeutic options in older women; conversely a pAkt1+/pE2F1− phenotype could prompt a more aggressive regimen. Further exploration of this phenotype in younger women with breast cancer and triple-negative breast cancers is warranted.

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References

  • Al-Bahlani SM, Al-Rashdi RM, Kumar S, Al-Sinawi SS, Al-Bahri MA, Shalaby AA (2017) Calpain-1 expression in triple-negative breast cancer: a potential prognostic factor independent of the proliferative/apoptotic index. BioMed Res Int 2017:9290425

    PubMed  PubMed Central  Google Scholar 

  • Arciero CA, Styblo TM (2018) Clinically established prognostic factors in breast cancer. In: The breast, 5th edn. Elsevier, Amsterdam, pp 250–257.e3

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424

    Article  Google Scholar 

  • Bianco R, Melisi D, Ciardiello F, Tortora G (2006) Key cancer cell signal transduction pathways as therapeutic targets. Eur J Cancer 42:290–294

    Article  CAS  Google Scholar 

  • Chen H-Z, Tsai S-Y, Leone G (2009) Emerging roles of E2Fs in cancer: an exit from cell cycle control. Nat Rev Cancer 9:785

    Article  CAS  Google Scholar 

  • Chien AJ, Tripathy D, Albain KS, Symmans WF, Rugo HS, Melisko ME et al (2020) MK-2206 and standard neoadjuvant chemotherapy improves response in patients with human epidermal growth factor receptor 2-positive and/or hormone receptor-negative breast cancers in the I-SPY 2 trial. J Clin Oncol 38:1059–1069

    Article  CAS  Google Scholar 

  • Cicenas J (2008) The potential role of Akt phosphorylation in human cancers. Int J Biol Markers 23:1–9

    Article  CAS  Google Scholar 

  • Coffer PJ, Jin J, Woodgett JR (1998) Protein kinase B (c-Akt): a multifunctional mediator of phosphatidylinositol 3-kinase activation. Biochem J 335:1

    Article  CAS  Google Scholar 

  • Dai H, Li M, Yang W, Sun X, Wang P, Wang X et al (2020) Resveratrol inhibits the malignant progression of hepatocellular carcinoma via MARCH1-induced regulation of PTEN/AKT signaling. Aging (Albany NY) 12:11717–11731

    Article  CAS  Google Scholar 

  • Hallstrom TC, Mori S, Nevins JR (2008) An E2F1-dependent gene expression program that determines the balance between proliferation and cell death. Cancer Cell 13:11–22

    Article  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  Google Scholar 

  • Ho GH, Calvano JE, Bisogna M, Van Zee KJ (2001) Expression of E2F-1 and E2F-4 is reduced in primary and metastatic breast carcinomas. Breast Cancer Res Treat 69:115–122

    Article  CAS  Google Scholar 

  • Kaboli PJ, Salimian F, Aghapour S, Xiang S, Zhao Q, Li M et al (2020) Akt-targeted therapy as a promising strategy to overcome drug resistance in breast cancer—a comprehensive review from chemotherapy to immunotherapy. Pharmacol Res 156:104806

    Article  Google Scholar 

  • Kwon MJ, Nam ES, Cho SJ, Park HR, Shin HS, Park JH et al (2010) E2F1 expression predicts outcome in Korean women who undergo surgery for breast carcinoma. Ann Surg Oncol 17:564–571

    Article  Google Scholar 

  • Lal S, Reed AEM, de Luca XM, Simpson PT (2017) Molecular signatures in breast cancer. Methods 131:35–146

    Article  Google Scholar 

  • Liu K, Paik JC, Wang B, Lin FT, Lin WC (2006) Regulation of TopBP1 oligomerization by Akt/PKB for cell survival. EMBO J 25:4795–4807

    Article  CAS  Google Scholar 

  • Liu X, Jakubowski M, Hunt JL (2011) KRAS gene mutation in colorectal cancer is correlated with increased proliferation and spontaneous apoptosis. Am J Clin Pathol 135:245–252

    Article  CAS  Google Scholar 

  • Malinowski DP (2007) Multiple biomarkers in molecular oncology. II. Molecular diagnostics applications in breast cancer management. Expert Rev Mol Diagn 7:269–280

    Article  CAS  Google Scholar 

  • Mattern J, Volm M (2004) Imbalance of cell proliferation and apoptosis during progression of lung carcinomas. Anticancer Res 24:4243–4246

    PubMed  Google Scholar 

  • Neumayer L, Viscusi RK (2018) Assessment and designation of breast cancer stage. In: The breast, 5th edn. Elsevier, pp 531–552.e6

  • Nicholson KM, Anderson NG (2002) The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal 14:381–395

    Article  CAS  Google Scholar 

  • Patani N, Martin LA, Dowsett M (2013) Biomarkers for the clinical management of breast cancer: international perspective. Int J Cancer 133:1–13

    Article  CAS  Google Scholar 

  • Penault-Llorca F, Radosevic-Robin N (2017) Ki67 assessment in breast cancer: an update. Pathology 49:166–171

    Article  CAS  Google Scholar 

  • Pérez-Tenorio G, Stål O (2002) Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients. Br J Cancer 86:540

    Article  Google Scholar 

  • Poppy Roworth A, Ghari F, La Thangue NB (2015) To live or let die—complexity within the E2F1 pathway. Mol Cell Oncol 2:e970480

    Article  CAS  Google Scholar 

  • Roser M, Ritchie H (2018) Cancer. The Institute for Health Metrics and Evaluation. Published online at OurWorldInData.org. https://ourworldindata.org/cancer. Accessed 15 May 2018

  • Song G, Ouyang G, Bao S (2005) The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med 9:59–71

    Article  CAS  Google Scholar 

  • Sun B, Wingate H, Swisher SG, Keyomarsi K, Hunt KK (2010) Absence of pRb facilitates E2F1-induced apoptosis in breast cancer cells. Cell Cycle 9:1122–1130

    Article  CAS  Google Scholar 

  • Testa JR, Bellacosa A (2001) AKT plays a central role in tumorigenesis. Proc Natl Acad Sci USA 98:10983–10985

    Article  CAS  Google Scholar 

  • Worku D, Jouhra F, Jiang G, Patani N, Newbold R, Mokbel K (2008) Evidence of a tumour suppressive function of E2F1 gene in human breast cancer. Anticancer Res 28:2135–2139

    CAS  PubMed  Google Scholar 

  • Yang Z-Y, Di M-Y, Yuan J-Q, Shen W-X, Zheng D-Y, Chen J-Z et al (2015) The prognostic value of phosphorylated Akt in breast cancer: a systematic review. Sci Rep 5:7758

    Article  CAS  Google Scholar 

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Acknowledgements

We thank the Immunohistochemistry Unit of Department of Pathology, Sultan Qaboos University Hospital, Sultan Qaboos University, Oman for the technical assistance in performing the immunostaining.

Funding

This work was supported by College of Medicine and Health Sciences, Sultan Qaboos University (Grant No. IG/MED/PATH/14/01). The funding body had no involvement in the design of the study, collection, analysis, and interpretation of data and in writing the manuscript.

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Authors and Affiliations

  1. Department of Allied Health Sciences, College of Medicine and Health Sciences, Sultan Qaboos University, Alkhoud, PC 123, P.O. Box 35, Muscat, Oman

    Shadia M. Al-Bahlani

  2. College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health Care City, Dubai, UAE

    Ritu Lakhtakia

  3. Department of Biology, College of Science, Sultan Qaboos University, Muscat, Oman

    Samiya S. Al-Jaaidi

  4. Department of Pathology, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Oman

    Shadia S. Al-Sinawi, Shaymaa G. Abd-Elmoety & Asem A. Shalaby

  5. Department of Hematology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman

    Murtadha Al-Khabori

  6. Oncology Unit, Department of Medicine, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Oman

    Anjum H. A. Osman & Khalid Al-Baimani

  7. Pathology Department, College of Medicine, Mansoura University, El Mansûra, Egypt

    Asem A. Shalaby

Authors
  1. Shadia M. Al-Bahlani
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  2. Ritu Lakhtakia
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  3. Samiya S. Al-Jaaidi
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  4. Shadia S. Al-Sinawi
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  5. Shaymaa G. Abd-Elmoety
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  6. Murtadha Al-Khabori
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  7. Anjum H. A. Osman
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  8. Khalid Al-Baimani
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  9. Asem A. Shalaby
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Correspondence to Shadia M. Al-Bahlani.

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Al-Bahlani, S.M., Lakhtakia, R., Al-Jaaidi, S.S. et al. Correlation of expression of Akt1 and E2F1 and their phosphorylated forms in breast cancer patients with clinicopathological parameters. J Mol Histol 52, 621–633 (2021). https://doi.org/10.1007/s10735-021-09973-1

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  • DOI: https://doi.org/10.1007/s10735-021-09973-1

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