Cancer Research and Treatment

Original Articles

Cell Cycle Regulatory Protein Expression Profiles by Adenovirus p53 Infection in Human Papilloma Virus-associated Cervical Cancer Cells: Yong-Seok Lee, Su-Mi Bae, Sun-Young Kwak, Dong-Chun Park, Yong-Wook Kim, Soo-Young Hur, Eun-Kyung Park, Byoung-Don Han, Young-Joo Lee, Chong-Kook Kim, Do Kang Kim, Woong-Shick Ahn; Cancer Res Treat. 2006;38(3):168-177. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.168

Purpose

The tumor suppressor gene, p53, has been established as an essential component for the suppression of tumor cell growth. In this study, we investigated the time-course anticancer effects of adenoviral p53 (Adp53) infection on human ovarian cancer cells to provide insight into the molecular-level understanding of the growth suppression mechanisms involved in Adp53-mediated apoptosis and cell cycle arrest.

Materials and Methods

Three human cervical cancer cell lines (SiHa, CaSki, HeLa and HT3) were used. The effect of Adp53 infection was studied via cell count assay, cell cycle analysis, FACS, Western blot and macroarray assay.

Results

Adp53 exerts a significant role in suppressing cervical cancer cell growth. Adp53 also showed growth inhibitory effects in each cell line, and it induced apoptosis and cell cycle arrest. Adp53 differentially regulated the expression of genes and proteins, and the gene expression profiles in the SiHa cells revealed that the p21, p53 and mdm2 expres sions were significantly up-regulated at 24 and 48 hr. Western blot shows that the p21 and p53 expression-levels were significantly increased after Adp53 infection. In addition, in all cell lines, both the CDK4 and PCNA protein expression levels were decreased 48 h after Adp53 infection. Cell cycle arrest at the G1 phase was induced only in the SiHa and HeLa cells, suggesting that exogenous infection of Adp53 in cancer cells was significantly different from the other HPV-associated cervical cancer cells.

Conclusion

Adp53 can inhibit cervical cancer cell growth through induction of apoptosis and cell cycle arrest, as well as through the regulation of the cell cycle-related proteins. The Adp53-mediated apoptosis can be employed as an advanced strategy for developing preferential tumor cell-specific delivery.

Citations

Citations to this article as recorded by

Health‐promoting bioactivity and in vivo genotoxicity evaluation of a hemiepiphyte fig, Ficus dubia
Uthaiwan Suttisansanee, Pornsiri Pitchakarn, Pisamai Ting, Woorawee Inthachat, Parunya Thiyajai, Daraphan Rodthayoy, Jirarat Karinchai, Bhanumas Chantarasuwan, Onanong Nuchuchua, Piya Temviriyanukul
Food Science & Nutrition.2021; 9(4): 2269. CrossRef
Comprehensive Data of P53 R282 Gene Mutation with Human Papillomaviruses (HPV)-Associated Oral Squamous Cell Carcinoma (OSCC)
Tipaya Ekalaksananan, Weerayut Wongjampa, Pensiri Phusingha, Jureeporn Chuerduangphui, Patravoot Vatanasapt, Supannee Promthet, Natcha Patarapadungkit, Chamsai Pientong
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Etoposide radiosensitizes p53-defective cholangiocarcinoma cell lines independent of their G2 checkpoint efficacies
Arunee Hematulin, Sutiwan Meethang, Kitsana Utapom, Sopit Wongkham, Daniel Sagan
Oncology Letters.2018;[Epub] CrossRef
Effect and Safety of Recombinant Adenovirus-p53 Transfer Combined with Radiotherapy on Long-Term Survival of Locally Advanced Cervical Cancer
Xing Su, Wen-juan Chen, Shao-wen Xiao, Xiao-fan Li, Gang Xu, Jian-ji Pan, Shan-wen Zhang
Human Gene Therapy.2016; 27(12): 1008. CrossRef
Celecoxib, a COX-2 Selective Inhibitor, Induces Cell Cycle Arrest at the G2/M Phase in HeLa Cervical Cancer Cells
Agustina Setiawati
Asian Pacific Journal of Cancer Prevention.2016; 17(4): 1655. CrossRef
Cisplatin sensitivity and mechanisms of anti-HPV16 E6-ribozyme on cervical carcinoma CaSKi cell line
Zhiguo Rao, Jianfei Gao, Bicheng Zhang, Bo Yang, Jiren Zhang
The Chinese-German Journal of Clinical Oncology.2012; 11(4): 237. CrossRef

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6 Crossref

Protein Expression Profile using Two-Dimensional Gel Analysis in Squamous Cervical Cancer Patients: Su-Mi Bae, Hyun-Jin Min, Guo Hua Ding, Sun-Young Kwak, Young-Lae Cho, Kye-Hyun Nam, Choong Hak Park, Yong-Wan Kim, Chong-Kook Kim, Byoung-Don Han, Young-Joo Lee, Do Kang Kim, Woong-Shick Ahn; Cancer Res Treat. 2006;38(2):99-107. Published online April 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.2.99

Abstract PDF PubReader ePub

Purpose

Screening in cervical cancer is now progressing to discover candidate genes and proteins that may serve as biological markers and that play a role in tumor progression. We examined the protein expression patterns of the squamous cell carcinoma (SCC) tissues from Korean women with using two- dimensional polyacrylamide gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization-time of flight (MALDI- TOF) mass spectrometer.

Materials and Methods

Normal cervix and SCC tissues were solubilized and 2-DE was performed using pH 3~10 linear IPG strips of 17 cm length. The protein expression was evaluated using PDQuest 2-D software™. The differentially expressed protein spots were identified with a MALDI-TOF mass spectrometer, and the peptide mass spectra identifications were performed using the Mascot program and by searching the Swiss-prot or NCBInr databases.

Results

A total of 35 proteins were detected in SCC. 17 proteins were up-regulated and 18 proteins weredown-regulated. Among the proteins that were identified, 12 proteins (pigment epithelium derived factor, annexin A2 and A5, keratin 19 and 20, heat shock protein 27, smooth muscle protein 22 alpha, α-enolase, squamous cell carcinoma antigen 1 and 2, glutathione S-transferase and apolipoprotein a1) were protein previously known to be involved in tumor, and 21 proteins were newly identified in this study.

Conclusion

2-DE offers the total protein expression profiles of SCC tissues; further characterization of these differentially expressed proteins will give a chance to identify the badly needed tumor-specific diagnostic markers for SCC.

Citations

Citations to this article as recorded by

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Tao Shen, Tingting Dong, Haiyang Wang, Yi Ding, Jianuo Zhang, Xinyi Zhu, Yeping Ding, Wen Cai, Yalan Wei, Qiao Wang, Sufen Wang, Feiyun Jiang, Bin Tang
BMC Cancer.2025;[Epub] CrossRef
The role of proteomics in the modern diagnosis of cervical cancer
Aida U. Hamadyanova, Azalia S. Sultanmuratova, Aliya Kh. Disbiyanova, Svetlana N. Akhmadeyeva, Nikita O. Yadgarov, Liana E. Burangulova
Journal of obstetrics and women's diseases.2022; 71(2): 113. CrossRef
Understanding Cervical Cancer through Proteomics
Fátima Martínez-Rodríguez, Jared E. Limones-González, Brenda Mendoza-Almanza, Edgar L. Esparza-Ibarra, Perla I. Gallegos-Flores, Jorge L. Ayala-Luján, Susana Godina-González, Eva Salinas, Gretel Mendoza-Almanza
Cells.2021; 10(8): 1854. CrossRef
Annexin A1 peptide and endothelial cell‐conditioned medium modulate cervical tumorigenesis
Laila Toniol Cardin, Janesly Prates, Bianca Rodrigues da Cunha, Eloiza Helena Tajara, Sonia Maria Oliani, Flávia Cristina Rodrigues‐Lisoni
FEBS Open Bio.2019; 9(4): 668. CrossRef
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Sapna Khowal, Samar H. Naqvi, Seema Monga, Swatantra K. Jain, Saima Wajid
Journal of Cellular Biochemistry.2018; 119(7): 5186. CrossRef
iTRAQ-based quantitative proteomic analysis of cervical cancer
YIBING DING, MIN YANG, SHA SHE, HAIYAN MIN, XIAOMING XV, XIAOPING RAN, YONGZHENG WU, WEI WANG, LEI WANG, LONG YI, YIXUAN YANG, QIAN GAO
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Role-Shifting PKCζ Fosters Its Own Proapoptotic Destruction by Complexing with Bcl10 at the Nuclear Envelope of Human Cervical Carcinoma Cells: A Proteomic and Biochemical Study
Anna Chiarini, Maddalena Marconi, Raffaella Pacchiana, Ilaria Dal Prà, Jun Wu, Ubaldo Armato
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Annexin A5 protein expression is associated with the histological differentiation of uterine cervical squamous cell carcinoma in patients with an increased serum concentration
XIN LI, LONG CHEN, XIU JUN LIANG, YU FENG GAO, XIAO JIE WANG, QIAN XU, YONG YAN, FU LU GAO
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Altered Carcinogenesis and Proteome in Mammary Glands of Rats after Prepubertal Exposures to the Hormonally Active Chemicals Bisphenol A and Genistein
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BMC Medical Genomics.2011;[Epub] CrossRef
α‐enolase: a promising therapeutic and diagnostic tumor target
Michela Capello, Sammy Ferri‐Borgogno, Paola Cappello, Francesco Novelli
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Glucose‐regulated protein 58 modulates cell invasiveness and serves as a prognostic marker for cervical cancer
Chia‐Jung Liao, Tzu‐I Wu, Ya‐Hui Huang, Ting‐Chang Chang, Chia‐Siu Wang, Ming‐Ming Tsai, Chyong‐Huey Lai, Ying Liang, Shih‐Ming Jung, Kwang‐Huei Lin
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Identification of Cervical Cancer Proteins Associated With Treatment With Paclitaxel and Cisplatin in Patients
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Immunization with Adenoviral Vectors Carrying Recombinant IL-12 and E7 Enhanced the Antitumor Immunity against Human Papillomavirus 16-associated Tumor: Eun-Kyung Park, Young-Wook Kim, Joon-Mo Lee, Sung-Eun NamKoong, Do-Gang Kim, Heung-Jae Chun, Byoung-Don Han, Su-Mi Bae, Hyun-Sun Jin, Jeong-Im Sin, Woong-Shick Ahn; Cancer Res Treat. 2005;37(1):63-70. Published online February 28, 2005; DOI: https://doi.org/10.4143/crt.2005.37.1.63

Abstract PDF PubReader ePub

Purpose

Human papillomavirus (HPV) infection has a significant role in cervical carcinogenesis, and HPV oncoprotein E7 plays an important part in the formation and maintenance of cervical cancer. Interleukin-12 (IL-12) has been reported to induce a cellular immune response, and to suppress the tumor growth and the E7 production. Here we describe the use of adenoviral delivery of the HPV 16 E7 subunit (AdE7) along with adenoviral delivery of IL-12 (AdIL-12) in mice with HPV-associated tumors.

Materials and Methods

Mice were injected with TC-1 cells to establish TC-1 tumor, and then they were immunized with AdIL-12 and/or AdE7 intratumorally. The anti tumor effects induced by AdIL-12 and/or E7 were evaluated by measuring the size of the tumor. E7-specific antibody and INF-γ production in sera, and the T-helper cell proliferative responses were then measured. Cytotoxic T-lymphocyte (CTL) and T cell subset depletion studies were also performed.

Results

Combined AdIL-12 and AdE7 infection at the tumor sites significantly enhanced the antitumor effects more than that of AdIL-12 or AdE7 single infection. This combined infection resulted in regression of the 9 mm sized tumors in 80% of animals as compare to the PBS group. E7-specific antibody and INF-γ production in the sera, and the T-helper cell proliferative responses were significantly higher with coinfection of AdIL-12 and AdE7 than with AdIL-12 or AdE7 alone. CTL response induced by AdIL-12 and AdE7 in the coinjected group suggested that tumor suppression was mediated by mostly CD8+ and only a little by the CD4+ T cells.

Conclusion

IL-12 and E7 application using adenovirus vector showed antitumor immunity effects against TC-1 tumor, and this system could be use in clinical applications for HPV-associated cancer. (ED note: nice abstract.)

Citations

Citations to this article as recorded by

Development of a replication‐deficient adenoviral vector‐based vaccine candidate for the interception of HPV16‐ and HPV18‐induced infections and disease
Selina Khan, Koen Oosterhuis, Kerstin Wunderlich, Evelien M. Bunnik, Melissa Bhaggoe, Satish Boedhoe, Santusha Karia, Renske D.M. Steenbergen, Leontien Bosch, Jan Serroyen, Sarah Janssen, Hanneke Schuitemaker, Jort Vellinga, Gert Scheper, Roland Zahn, Jer
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Jiarong Xu, Dongyan Huang, shichao Liu, Huixing Lin, Haodan Zhu, Bao Liu, Chengping Lu
Vaccine.2012; 30(20): 3119. CrossRef
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Jiarong Xu, Dongyan Huang, Shichao Liu, Huixing Lin, Haodan Zhu, Bao Liu, Chengping Lu
Virus Research.2012; 167(2): 188. CrossRef

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