Login Register Cart 0
Generic placeholder image

Current Proteomics

Editor-in-Chief

ISSN (Print): 1570-1646
ISSN (Online): 1875-6247

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Role of Cervical Cancer Radiotherapy in the Expression of EGFR and p53 Gene

Author(s): Yan Cheng, Kuntian Lan, Xiaoxia Yang, Dongxia Liang, Li Xia and Jinquan Cui*

Volume 17, Issue 1, 2020

Page: [23 - 29] Pages: 7

DOI: 10.2174/1570164616666190204155403

open access plus

Abstract

Background: Cervical cancer arises from the cervix and it is the 3rd most diagnosed malignancy and a foremost cause of cancer-related death in females. On the other hand, the expressions of EGFR and p53 are two important proteins observed in various studies on cervical cancer.

Objective: The study aims to evaluate the beneficial effect of radiotherapy based on the regulation of p53 and EGFR gene in patients with cervical cancer.

Methods: In this investigation, the regulation of important molecules responsible for cancer cell proliferation and DNA repair in the cervical cancer cell line was evaluated. The study comprises of an evaluation based on clinical study design from the malignant biopsies of 15 cervical cancer patients. The patterns of expression for the p53 gene and Epidermal Growth Factor Receptor (EGFR) were evaluated in DoTc2 and SiHa cervical cancer cell lines using clonogenic assay, western blotting and immunohistochemistry techniques from the malignant biopsies of the 15 patients.

Results: The study observed that the regulation of p53 and EGFR was very weak after the exposure of the radiation. In addition, the expression of p53 and EGFR was observed in malevolent biopsy samples after radiation with a dosage of 1.8 Gy radiations. Additionally, the expression of p53 and EGFR was able to induce by a single dose of radiotherapy in the malignant biopsies whereas it was unable to induce in DoTc2 and SiHa cervical cancer cells.

Conclusion: The study observed that radiation exposed cancer cell lines modulates the expression of p53 and EGFR gene. The study also highlights the gap between in vitro experimental models and clinical study design.

Keywords: Cervical cancer, cell line, p53, EGFR, malignancy, human papillomavirus (HPV).

« Previous Next »
Graphical Abstract

[1]
Scolnick, E.M. A vaccine to prevent cervical cancer: Academic and industrial collaboration and a Lasker award. Clin. Transl. Immunology, 2017, 28e1002
[2]
Jung, K.W.; Won, Y.J.; Kong, H.J.; Lee, E.S. Prediction of cancer incidence and mortality in Korea, 2018. Cancer Res. Treat., 2018, 50(2), 317-323.
[3]
Mukama, T.; Ndejjo, R.; Musabyimana, A.; Halage, A.A.; Musoke, D. Women’s knowledge and attitudes towards cervical cancer prevention: A cross sectional study in Eastern Uganda. BMC Womens Health, 2017, 17(1), 9-18.
[4]
Chatterjee, S.; Chattopadhyay, A.; Samanta, L.; Panigrahi, P. HPV and cervical cancer epidemiology - current status of HPV vaccination in India. Asian Pac. J. Cancer Prev., 2016, 17(8), 3663-3673.
[5]
Serkies, K.; Jassem, J. Systemic therapy for cervical carcinoma - current status. Chin. J. Cancer Res., 2018, 30(2), 209-221.
[6]
Naga, C.P.; Gurram, L.; Chopra, S.; Mahantshetty, U. The management of locally advanced cervical cancer. Curr. Opin. Oncol., 2018, 30(5), 323-329.
[7]
Zhu, S.; Zhu, J.; Song, Y.; Chen, J.; Wang, L. Bispecific affibody molecule targeting HPV16 and HPV18E7 oncoproteins for enhanced molecular imaging of cervical cancer. Appl. Microbiol. Biotechnol., 2018, 102(17), 7429-7439.
[8]
Martínez-Ramírez, I.; Carrillo-García, A.; Contreras-Paredes, A.; Ortiz-Sánchez, E.; Cruz-Gregorio, A.; Lizano, M. Regulation of cellular metabolism by high-risk human papillomaviruses. Int. J. Mol. Sci., 2018, 19(7) pii: E1839
[9]
Zhang, W.; Jiang, Y.; Yu, Q.; Qiang, S.; Liang, P.; Gao, Y.; Zhao, X.; Liu, W.; Zhang, J. EGFR promoter methylation, EGFR mutation, and HPV infection in Chinese cervical squamous cell carcinoma. Appl. Immunohistochem. Mol. Morphol., 2015, 23(9), 661-666.
[10]
He, C.; Mao, D.; Hua, G.; Lv, X.; Chen, X.; Angeletti, P.C.; Dong, J.; Remmenga, S.W.; Rodabaugh, K.J.; Zhou, J.; Lambert, P.F.; Yang, P.; Davis, J.S.; Wang, C. The Hippo/YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression. EMBO Mol., 2015, 7(11), 1426-1449.
[11]
Kong, L.; Hao, Q.; Wang, Y. Regulation of p53 expression and apoptosis by vault RNA2-1-5p in cervical cancer cells. Oncotarget, 2015, 6(29), 28371-28388.
[12]
Xiao, S.; Zhou, Y.; Yi, W.; Luo, G.; Jiang, B.; Tian, Q.; Li, Y.; Xue, M. Fra-1 is downregulated in cervical cancer tissues and promotes cervical cancer cell apoptosis by p53 signaling pathway in vitro. Int. J. Oncol., 2015, 46(4), 1677-1684.
[13]
Franken, N.A.; Rodermond, H.M.; Stap, J.; Haveman, J.; van Bree, C. Clonogenic assay of cells in vitro. Nat. Protoc., 2006, 1(5), 2315-2319.
[14]
Gadducci, A.; Guerrieri, M.E.; Greco, C. Tissue biomarkers as prognostic variables of cervical cancer. Crit. Rev. Oncol. Hematol., 2013, 86(2), 104-129.
[15]
Rishi, K.S.; Alva, R.C.; Kadam, A.R.; Sharma, S. Outcomes of computed tomography-guided image-based interstitial brachytherapy for cancer of the cervix using GEC-ESTRO guidelines. Indian J. Surg. Oncol., 2018, 9(2), 181-186.
[16]
Tsvetkov, P.; Adler, J.; Myers, N.; Biran, A.; Reuven, N.; Shaul, Y. Oncogenic addiction to high 26S proteasome level. Cell Death Dis., 2018, 9(7), 773.
[17]
Cornelison, R.; Dobbin, Z.C.; Katre, A.A.; Jeong, D.H.; Zhang, Y.; Chen, D.; Petrova, Y.; Llaneza, D.C.; Steg, A.D.; Parsons, L.; Schneider, D.A.; Landen, C.N. Targeting RNA-polymerase I in both chemosensitive and chemoresistant populations in epithelial ovarian cancer. Clin. Cancer Res., 2017, 23(21), 6529-6540.
[18]
de Almeida, V.H.; de Melo, A.C.; Meira, D.D.; Pires, A.C.; Nogueira-Rodrigues, A.; Pimenta-Inada, H.K.; Alves, F.G.; Moralez, G.; Thiago, L.S.; Ferreira, C.G.; Sternberg, C. Radiotherapy modulates expression of EGFR, ERCC1 and p53 in cervical cancer. Braz. J. Med. Biol. Res., 2017, 51(1)e6822
[19]
Sun, X.; Li, Q. Prostaglandin EP2 receptor: Novel therapeutic target for human cancers. Int. J. Mol. Med., 2018, 42(3), 1203-1214.
[20]
Holley, A.K.; Miao, L.; St Clair, D.K.; St Clair, W.H. Redox-modulated phenomena and radiation therapy: The central role of superoxide dismutases. Antioxid. Redox Signal., 2014, 20(10), 1567-1589.
[21]
Alarcón, R.; Koumenis, C.; Geyer, R.K.; Maki, C.G.; Giaccia, A.J. Hypoxia induces p53 accumulation through MDM2 down-regulation and inhibition of E6-mediated degradation. Cancer Res., 1999, 59, 6046-6051.
[22]
Mai, K.T. Does differentiated squamous intraepithelial neoplasia occur in the cervix? Appl. Immunohistochem. Mol. Morphol., 2018, 26(4), e52-e60.
[23]
Shukla, S.; Dass, J.; Pujani, M. p53 and bcl2 expression in malignant and premalignant lesions of uterine cervix and their correlation with human papilloma virus 16 and 18. South Asian J. Cancer, 2014, 3, 48-53.
[24]
Pflaum, J.; Schlosser, S.; Müller, M. p53 family and cellular stress responses in cancer. Front. Oncol., 2014, 21, 285-294.
[25]
Thomas, N.B.; Hutcheson, I.R.; Campbell, L.; Gee, J.; Taylor, K.M.; Nicholson, R.I.; Gumbleton, M. Growth of hormone-dependent MCF-7 breast cancer cells is promoted by constitutive caveolin-1 whose expression is lost in an EGF-R-mediated manner during development of tamoxifen resistance. Breast Cancer Res. Treat., 2010, 119(3), 575-591.
[26]
So, D.; Shin, H.W.; Kim, J.; Lee, M.; Myeong, J.; Chun, Y.S.; Park, J.W. Cervical cancer is addicted to SIRT1 disarming the AIM2 antiviral defense. Oncogene, 2018, 37(38), 5191-5204.
[27]
Christopher, L.B.; Wei, G. Anti-aging protein SIRT1: A role in cervical cancer? Aging (Albany NY), 2009, 1(3), 278-280.
[28]
Li, D.; Wu, Q.J.; Bi, F.F.; Chen, S.L.; Zhou, Y.M.; Zhao, Y.; Yang, Q. Effect of the BRCA1-SIRT1-EGFR axis on cisplatin sensitivity in ovarian cancer. Am. J. Transl. Res., 2016, 8(3), 1601-1608.
[29]
Tian, W.J.; Huang, M.L.; Qin, Q.F.; Chen, Q.; Fang, K.; Wang, P.L. Prognostic impact of epidermal growth factor receptor overexpression in patients with cervical cancer: A meta analysis. PLoS One, 2016, 11e0158787
[30]
Yacoub, A.; McKinstry, R.; Hinman, D. Chung, T.; Dent, P.; Hagan, M.P. Epidermal growth factor and ionizing radiation up-regulate the DNA repair genes XRCC1 and ERCC1 in DU145 and LNCaP prostate carcinoma through MAPK signaling. Radiat. Res., 2003, 159, 439-452.
[31]
Schaue, D.; McBride, W.H. Opportunities and challenges of radiotherapy for treating cancer. Nat. Rev. Clin. Oncol., 2015, 12(9), 527-540.

Rights & Permissions Print Cite
Article Metrics
28
© 2024 Bentham Science Publishers | Privacy Policy