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Review Article
The Role of HPV E6 and E7 Oncoproteins in HPV-associated Cervical Carcinogenesis
Eun-Kyoung Yim, Jong-Sup Park
Cancer Res Treat. 2005;37(6):319-324.   Published online December 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.6.319
AbstractAbstract PDFPubReaderePub

Cervical cancer is one of the leading world causes of cancer morbidity and mortality in woman, with more than 98% related to a human papillomavirus (HPV) infection origin. Infection with specific subtypes of HPV has been strongly implicated in cervical carcinogenesis. The identification and functional verification of host proteins associated with HPV E6 and E7 oncoproteins may provide useful information in understanding cervical carcinogenesis and the development of cervical cancer-specific markers. The advent of functional genomics and proteomics has provided hope of discovering novel biological markers for use in the screening, early diagnosis, prognostication and prediction of response to therapy. Herein, we review the studies where the profiles of host proteins associated with HPV E6 and E7 oncoproteins in cervical cancer were generated.

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    Journal of the Egyptian National Cancer Institute.2013; 25(2): 87.     CrossRef
  • Canine distemper virus induces apoptosis in cervical tumor derived cell lines
    Helen L Del Puerto, Almir S Martins, Amy Milsted, Elaine M Souza-Fagundes, Gissandra F Braz, Barbara Hissa, Luciana O Andrade, Fabiana Alves, Daniela S Rajão, Rômulo C Leite, Anilton C Vasconcelos
    Virology Journal.2011;[Epub]     CrossRef
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Original Articles
Tetraarsenic Oxide-mediated Apoptosis in a Cervical Cancer Cell Line, SiHa
Jeong Kim, Su-Mi Bae, Dae-Seog Lim, Sun-Young Kwak, Chang-Ki Lee, Yong-Seok Lee, IL-Ju Bae, Jin-Young Yoo, Young-Joo Lee, Chong-Kook Kim, Woong-Shick Ahn
Cancer Res Treat. 2005;37(5):307-312.   Published online October 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.5.307
Retraction in: Cancer Res Treat 2007;39(1):48
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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
AbstractAbstract PDFPubReaderePub
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
    International Journal of Cancer.2017; 141(2): 393.     CrossRef
  • Immune responses and protective efficacy of a recombinant swinepox virus expressing HA1 against swine H1N1 influenza virus in mice and pigs
    Jiarong Xu, Dongyan Huang, shichao Liu, Huixing Lin, Haodan Zhu, Bao Liu, Chengping Lu
    Vaccine.2012; 30(20): 3119.     CrossRef
  • Immune responses and protection efficacy of a recombinant swinepox virus expressing HA1 against swine H3N2 influenza virus in mice and pigs
    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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Clinical Implications of VEGF and p53 Expression in Squamous Cell Carcinoma of the Cervix Treated with Radiation Therapy
Jin Oh Kang, Seong Eon Hong, Dong Wook Kang
Cancer Res Treat. 2003;35(5):440-444.   Published online October 31, 2003
DOI: https://doi.org/10.4143/crt.2003.35.5.440
AbstractAbstract PDF
PURPOSE
The present study was designed to analyze the relationship between vascular endothelial growth factor (VEGF) and p53, and their impact on clinical outcome in squamous cell carcinoma of the cervix treated with radiation therapy. MATERIALS AND METHODS: This immunohistochemical study involved 23 patients with available paraffin blocks among 46 patients who were treated during the period from 1994 to 1997 in Eulji University Hospital in Korea. Anti-VEGF mouse monoclonal antibody and DO-7 anti- p53 mouse monoclonal antibody were used as the primary antibodies. Antibody binding was detected with a LSAB kit. Staining was defined as positive for VEGF and p53, when more than 10% and 5% of the tumor cells were stained out of 500 cells counted, respectively. RESULTS: FIGO stage (p=0.05) and tumor size (p=0.04) were significant prognostic factors for survival. p53 expression was present in 17 (77%) cases. There was no significant relationship between p53 staining and the clinicopathologic factors, such as FIGO stage (p=0.98), tumor size (p=0.43), lymph node status (p=0.82), parametrial invasion (p=0.96), and age (p=0.18). The five year survival rates according to the p53 expression status were 80% for the p53 negative group and 66% for the p53 positive group (p=0.58). Positive VEGF expression was observed in 11 (47%) of the total of 23 patients. Statistical evaluation of VEGF expression according to stage (p=0.36), tumor size(p=0.11), lymph node status (p=0.82), parametrial invasion (p=0.49), and age (p=0.55) revealed no significant difference in any of these parameters. The five year survival rates according to the VEGF expression status were 89% for the VEGF negative group and 41% for the VEGF positive group (p=0.07). CONCLUSION: We suggest that VEGF expression may have an effect on the prognosis of cervix cancer patients treated with radiation therapy, and further evaluation with a large sample size is warranted.

Citations

Citations to this article as recorded by  
  • Research advances in signaling pathways related to the malignant progression of HSIL to invasive cervical cancer: A review
    Huifang Wang, Chang Liu, Keer Jin, Xiang Li, Jiaxin Zheng, Danbo Wang
    Biomedicine & Pharmacotherapy.2024; 180: 117483.     CrossRef
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Alterations in Promoter Usage and Expression Levels of Insulin-like Growth Factor-II and H19 Genes in Cervical and Endometrial Cancer
Chan Lee, Seung Jo Kim, Joong Yol Na, Chang Suk Park, Sun Young Lee, In Ho Kim, Yu Kyoung Oh
Cancer Res Treat. 2003;35(4):314-322.   Published online August 31, 2003
DOI: https://doi.org/10.4143/crt.2003.35.4.314
AbstractAbstract PDF
PURPOSE
The biallelic expression of insulin-like growth factor-II (IGF2) and H19 has been reported to be associated with the progression of several tumors. Here, the promoter usage and expression levels of IGF2 and H19 are reported to be altered in cervical and endometrial cancers showing loss of imprinting (LOI).
MATERIALS AND METHODS
The imprinting status of IGF2 and H19 was examined in 32 cervical carcinomas, their matched normal tissues, 13 endometrial cancer and 33 normal endometrial tissues.
RESULTS
The LOI of IGF2 was observed in 7 of 18 (39%) and 1 of 13 (8.3%) informative cervical carcinomas and informative endometrial cancers, respectively. The LOI of the H19 gene was detected in 5 of 14 (36%) and in all 11 (100%) informative cervical carcinoma cases and informative endometrial cancer cases, respectively. The use of promoter P1 was observed in the LOI tumors of IGF2, but not in the tumors showing maintenance of IGF2 imprinting (MOI), or in cervical and endometrial cancers. Unlike MOI tumors, some LOI tumors revealed a lack of IGF2 transcription from the promoter P3. The LOI tumors of IGF2 showed increased expression of the IGF2 level, but a down-regulation of the H19, relative to normal tissues, whereas the MOI tumors revealed no significant alterations.
CONCLUSION
These results suggest that the promoter P1 could be involved in the biallelic expression of IGF2, and that the altered expression of the IGF2 and H19 levels might be associated with the progression of cervical and endometrial cancers that exhibit biallelic IGF2 expression.

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  • Long Noncoding RNA Mediated Regulation in Human Embryogenesis, Pluripotency, and Reproduction
    Lei Liu, Fang Fang, Xinyi Lu
    Stem Cells International.2022; 2022: 1.     CrossRef
  • Adherence to Cancer Prevention Guidelines and Endometrial Cancer Risk: Evidence from a Systematic Review and Dose-Response Meta-analysis of Prospective Studies
    Hui Sun, Qing Chang, Ya-Shu Liu, Yu-Ting Jiang, Ting-Ting Gong, Xiao-Xin Ma, Yu-Hong Zhao, Qi-Jun Wu
    Cancer Research and Treatment.2021; 53(1): 223.     CrossRef
  • The Role of Long Non-Coding RNAs (lncRNAs) in Female Oriented Cancers
    Faiza Naz, Imran Tariq, Sajid Ali, Ahmed Somaida, Eduard Preis, Udo Bakowsky
    Cancers.2021; 13(23): 6102.     CrossRef
  • Deregulation of H19 is associated with cervical carcinoma
    Anirban Roychowdhury, Sudip Samadder, Pijush Das, Dipanjana Indra Mazumder, Ankita Chatterjee, Sankar Addya, Ranajit Mondal, Anup Roy, Susanta Roychoudhury, Chinmay Kumar Panda
    Genomics.2020; 112(1): 961.     CrossRef
  • PIM protein kinases regulate the level of the long noncoding RNA H19 to control stem cell gene transcription and modulate tumor growth
    Neha Singh, Sathish K. R. Padi, Jeremiah J. Bearss, Ritu Pandey, Koichi Okumura, Himisha Beltran, Jin H. Song, Andrew S. Kraft, Virginie Olive
    Molecular Oncology.2020; 14(5): 974.     CrossRef
  • An updated review of the H19 lncRNA in human cancer: molecular mechanism and diagnostic and therapeutic importance
    Behnam Alipoor, Seyedeh Nasrin Parvar, Zolfaghar Sabati, Hamid Ghaedi, Hassan Ghasemi
    Molecular Biology Reports.2020; 47(8): 6357.     CrossRef
  • Advances of Long Noncoding RNAs-mediated Regulation in Reproduction
    Kang-Sheng Liu, Tai-Ping Li, Hua Ton, Xiao-Dong Mao, Ya-Jun Chen
    Chinese Medical Journal.2018; 131(2): 226.     CrossRef
  • Dysregulated expression of long noncoding RNAs in gynecologic cancers
    Elahe Seyed Hosseini, Matthieu Meryet-Figuiere, Hamed Sabzalipoor, Hamed Haddad Kashani, Hossein Nikzad, Zatollah Asemi
    Molecular Cancer.2017;[Epub]     CrossRef
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Cell-Specific Growth Inhibition of Human Cervical Cancer Cell by Recombinant Adenovirus p53 in vitro and in vivo
Su Mi Bae, Yong Wook Kim, Joo Hee Yoon, Jin Young Yoo, Young Seok Seo, Sang Lyun Nam, Joon Mo Lee, Sung Eun Namkoong, Chong Kook Kim, Yong Wan Kim, Woong Shick Ahn
Cancer Res Treat. 2003;35(3):181-190.   Published online June 30, 2003
DOI: https://doi.org/10.4143/crt.2003.35.3.181
AbstractAbstract PDF
PURPOSE
Despite the significance of the p53 adenoviral vector in cancer gene therapy, an advanced strategy for the development of preferential tumor cell-specific delivery and the long-term persistent gene expression control of p53 are required. In this study, the time-course expression patterns of p53 and E6, on cervical cancer cells, were investigated to obtain a molecular level understanding of the cell-dependent tumor growth suppression effects of a recombinant adenovirus expressing p53, both in vitro and in vivo. MATERIALS AND METHODS: The expressions of p53 and E6 in CaSki, SiHa, HeLa, HeLaS3, C33A and HT3 cervical cancer cell lines were examined. After infection with AdCMVp53, the cell growth inhibition was studied via cell count, MTT and Neutral red assays. After transfecting the AdCMVp53 and AdCMVLacZ into the cancer cells-xenografted nude mice, the anti-tumor effects were investigated for one month. RESULTS: The p53 protein levels were more notably expressed in the CaSki and HeLa than in the SiHa and HeLaS3 On day 6, the p53 was only detected in the HeLaS3. In contrast, the p53 expression was highly maintained in the C33A and HT3. The E6 mRNA levels gradually decreased in only the CaSki and HeLa. The growth suppression effects also showed cell-dependent patterns, which were consistent with the reciprocal expression patterns of p53 and E6. After transfection of the AdCMVp53, into the CaSki- and SiHa-xenografted nude mice, the tumor size was remarkably decreased in the SiHa cells as compared to that in the AdCMVLacZ transfected mice, indicating cell-specific growth inhibition patterns.
CONCLUSION
The adenovirus-mediated p53 gene transfection was very effective both in vitro and in vivo. Also, the anti-tumor effects were accomplished via the differential role of p53-specific apoptotic cell death, which was dependent on the cervical cancer cell line.

Citations

Citations to this article as recorded by  
  • 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 Research and Treatment.2005; 37(1): 63.     CrossRef
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Significance of p53 Immunoreactivity in Squamous Cell Carcinoma of the Cervix Treated with Radiotherapy Alone
Sung Ja Ahn, Ho Sun Choi, Chan Choi, Byung Sik Nah, Woong Ki Chung, Taek Keun Nam
J Korean Cancer Assoc. 2001;33(2):106-112.
AbstractAbstract PDF
PURPOSE
We undertook this study to evaluate the significance of p53 immunoreactivity in squamous cell carcinoma of the cervix, treated with radiotherapy alone.
MATERIALS AND METHODS
Immunohistochemical staining of p53 proteins were performed in eighty patients with squamous cell carcinoma of the cervix, and who completed curative radiotherapy between Jan. 1996 and Apr. 1998 at the Department of Therapeutic Radiology, Chonnam National University Hospital. External- beam radiotherapy was combined with intracavitary brachytherapy. Results were analyzed for the end points of pelvic tumor control and distant failure rates. The follow-up time ranged from 7 to 58 months with a median of 40 months.
RESULTS
p53 positive and negative groups involved 45 and 35 patients, respectively, and the positive p53 immunoreactivity rate was 56% (45/80). p53 immunoreactivity showed no significant correlation with age, tumor size, serum tumor marker (SCC), or HPV18 expression, while there was a statistically marginally significant correlation with HPV16 expression. The pelvic tumor control rate of the p53 positive group was 87% and that of p53 negative group was 83% (0.05). The other parameters influencing negatively to the pelvic tumor control and with statistical significance were tumor ulceration and barrel type. Multivariate analysis also showed that p53 immunoreactivity had no prognostic value for pelvic tumor control of the disease, and that the statistically significant factor was tumor ulceration. The treatment failure rate of the p53 positive group was 23% and that of the negative group was 26% (p>0.05).
CONCLUSION
p53 immunoreactivity in the cervix cancer stage IB, II patients seems to have no value as a predictor of tumor behavior after curative radiotherapy.
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Results of Radio-thermotherapy in Stage IIIb Uterine Cervical Cancer Local response, survival rate and analysis of prognostic factor
Chang Woo Moon
J Korean Cancer Assoc. 2000;32(4):714-723.
AbstractAbstract PDF
PURPOSE
This retrospective study was conducted to obtain local response and survival rates, and to analyze prognostic factors affecting survival of patients treated with radio-thermotherapy for stage IIIb uterine cervical cancer.
MATERIALS AND METHODS
From May 1992 to Dec. 1996, 24 patients treated with radio-thermo therapy for stage IIIb uterine cervical cancer at department of Radiation Oncology in Kosin Medical College, Kosin University were enrolled. Radiotherapy used 6~10 MV linear accelerator was performed in whole pelvis with 4 portals box technique by conventional (180~200 cGy/ fraction, 5 fraction/week) method in 5 patients (20.8%) or hyperfractionated (120~135 cGy/fr., 2 fr./day, 10 fr./wk) in 19 patients (79.2%). Total dose of A-point was 67~112 Gy (median: 77.27 Gy). Hyperthermia used 8 MHz radiofrequency capacitive heating device was applied in pelvic area with 2~3 sessions per wk. Each course started within 15 to 20 minutes after radio therapy and took 40 to 60 minutes. Local progression free (LPFS), disease free (DFS) and overall (OS) rates were calculated in survival analysis. Statistics was calculated by Kaplan-Meier Method in survival and Log-rank test in statistical significance. Multivariate analysis for prognostic factor was applied to Cox Regression model. Follow-up duration was 6~82 months (median: 25 months).
RESULTS
Overall local response rate was 95.8% (45.8% in CR/50.0% in PR). Five year LPFS, DFS, OS were 48.6%, 31.7%, 67.1%, respectively. In univariate analysis, an age was the signi ficant prognostic factor in terms of OS (p=0.03), but was insignificant in LPFS and DFS. In multivariate analysis, none of evaluated factors are important in LPFS, DFS or OS.
CONCLUSION
Radio-thermotherapy for stage IIIb uterine cervical cancer did not increase 5 year LPFS, DFS and OS in spite of higher local response rate. Age was the only significant factor for OS in univariate analysis.
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The Inefficiency of Routine Performance of a Batch of Tests in the Clinical Staging Work-up of Cervical Carcinoma
Soon Sup Shim, Jae Weon Kim, Yong Beom Kim, Ju Won Rho, Chul Min Lee, Noh Hyun Park, Yong Sang Song, Soon Beom Kang, Hyo Pyo Lee
J Korean Cancer Assoc. 2000;32(4):705-713.
AbstractAbstract PDF
PURPOSE
This study was to evaluate the efficiency of routine performance of a batch of tests in the clinical staging work-up of cervical carcinoma.
MATERIALS AND METHODS
The medical records were reviewed for 1,393 consecutive cervical carcinoma patients who underwent pretreatment staging work-up in Seoul National University Hospital from January 1988 to December 1997. The impression stage -which is designated ten tatively by the findings of pelvic examination and biopsy-, the results of staging work-up, and the finally allotted FIGO clinical stage were reviewed. The annual trend of stage distribution and the positive yields of tests were evaluated.
RESULTS
Annual trend shows that Ia is increasing. The positive yield of chest x-ray was 0.22% (3/1, 379; Ib: 1, IIa: 1, IIb: 1), intravenous pyelography (IVP) 2.50% (31/1, 242; Ib: 2, IIa: 4, IIb: 17, IIIb: 8), cystoscopy 0.55% (6/1, 093; IIb: 4, IIIb: 2), and proctosigmoidoscopy 0.086% (1/1, 157; Ib: 1). After completing the staging work-up, 29 patients (2.08%) were upstaged. The routine performance of IVP in impression stage Ia and cystoscopy in impression stage IIa or less was considered inefficient. The routine performance of proctosigmoidoscopy was considered inefficient because of its very low yield.
CONCLUSION
The selective performance of tests according to the impression stage during staging work-up is recommended to minimize the unnecessary treatment delay, cost, and patients' discomfort.
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Clinical Significance of Apoptosis and p53 Protein Expression in Stage IIB Squamous Cell Carcinoma of the Cervix Treated with Radiotherapy Alone
Eun Ji Chung, Gwi Eon Kim, Jinsil Seong, Woo Ick Yang, Young Tae Kim, Chang Ok Suh
J Korean Cancer Assoc. 2000;32(3):638-646.
AbstractAbstract PDF
PURPOSE
The purpose was to investigate the spontaneous apoptotic index (SAI) and p53 protein expression and to identify the role of SAI and p53 protein positivity.
MATERIALS AND METHODS
Forty six patients with squamous cell carcinoma of the cervix, FIGO stage IIB, treated with curative radiotherapy alone between 1990 and 1993 were included in this study. Definitive radiotherapy including external beam and high-dose-rate brachytherapy was given. Pretreatment paraffin-embedded biopsy specimens of those patients were scored for apoptosis and p53 protein expression using mouse mondegrees Clonal antibody (DO-7) by immuno staining. Clinicopathologic characteristics were also studied in relation to SAI and p53 protein expression, and as prognostic factors for clinical outcome.
RESULTS
SAI and p53 were not related to any clinical characteristics. The range of the SAI was 0.2~4.7% (median 1.1%, mean 1.5%). The rate of p53 protein expression was 65.2% (30/46). Patients whose tumors had high SAI and low p53 protein positivity had better treatment outcome than those with lower SAI. There was also a significant correlation between the SAI and p53 protein expression.
CONCLUSION
The pretreatment SAI and p53 oncoprotein expression are clinically useful in predicting the clinical outcome of FIGO stage IIB squamous cell carcinoma of the uterine cervix patients treated with definitive radiotherapy.
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Expressions of Cell Cycle Control Genes in Human Uterine Cervical Cancer Cells
Jung Geol Ahn, Tae Seong Lee, Jae We Cho, Won Ki Baek, Seong Il Suh, Min Ho Suh, Jong Wook Park, Soon Do Cha
J Korean Cancer Assoc. 2000;32(1):110-119.
AbstractAbstract PDF
PURPOSE
Recently, many aspects of biological functions of cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors and Rb gene have been reported, and the cell cycle control genes are considered to act important roles in tumorigenesis. In this study, the expression patterns of major cell cycle control genes (cyclin A, B, C, Dl, E, E2F, p16INK4a, p21WAF1 and Rb) in various human cervical cancer cells were analysed to elucidate the impacts of the cell cycle control genes on the carcinogenesis of human cervical cancer.
MATERIALS AND METHODS
The expression patterns of major cell cycle control genes in HT-3, C33-A, HeLa, C4-II, SiHa and CaSki human uterine cervical cancer cells were analysed by using western blot and reverse transcription-polymerase chain reaction (RT-PCR).
RESULTS
In most of the cervical cancer cells tested, the overexpressions of cyclin A, E, E2F and markedly decreased expression of Rb tumor suppressor proteins were observed. By comparing RNA and protein expressions in each cancer cells, the mechanisms of increased expressions of cyclin A, E and decreased expression of Rb were elucidated as post-translational controls.
CONCLUSION
The cervical carcinogenesis caused by the altered expressions of the major cell cycle control genes can be hypothesized as follows: overexpressions of cyclin E and A cause acceleration of Rb phosphorylations and E2F overexpression; increased E2F function accelerates G1/S transition of the cells; compensatory increase of p16 expression cannot stop the cells in Gl phase because Rb expression is severely decreased; consequently, loss of Rb function, 61 shortening, inappropriate cell division and decreased function of the maintenance of genomic stability occur. In addition to these alterations, loss of p53 functions further accelerate instability of genome and decrease the sus- ceptability to cell death. Furthermore, overexpression of Bc12 protects these abnormal cells from apoptosis. All these derangements of cell cycle control should contribute to the human cervical carcinogenesis.
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Detection of Human Papillomavirus DNA and p53 , p21 Gene Expression in CIN3 and Uterine Cervical Cancer
Jae Hyung Na, Ho Sun Choi
J Korean Cancer Assoc. 2000;32(1):100-109.
AbstractAbstract PDF
PURPOSE
Though the etiology of this cancer has not been elucidated, it has been suggested that certain types of human papillomavirus (HPV) and alteration of the p53 gene are closely associated with uterine cervical cancer. The aim of the study was to investigate the role of high risk HPV, p53 and p21 gene in cervical intraepithelial neoplasia III (CIN3) and invasive squamous cell carcinoma.
MATERIALS AND METHODS
The presence of high-risk HPV DNA (16, 18, 31, 33, 35, 45, 51, 52, 56) were detected from cervical swab in 240 patients by hybrid capture method. Expression of p53 genes were studied in paraffin-embedded specimens by immunohisto- chemical staining and p53, p21 gene alteration by RT-PCR SSCP using fresh cervical tissues.
RESULTS
High risk HPV DNA were detected in 34%, 74.3% and 75.7% in control, CIN3 and invasive squamaus cell carcinoma respectively. In patients with high risk HPV DNA, type 16 were detected of 5.9%, 30.8%, 47.2% respectively. Relative concentration of HPV DNA to control was 16.3+-27.4 in CIN3 and 30.4+-40.8 in invasive squamous cell cancer. Of patients with high risk HPV DNA, p53 expression was found in 42.9% of CIN3 immunohistochemically, while patients with invasive squamous cell carcinoma was de- tected in 50%. In patients without high risk HPV DNA, p53 expression was detected in 17.1% in CIN3, 15.7% in invasive squamous cell carcinoma. But the mutation of p53 and p21 gene by RT-PCR SSCP were not observed in CIN3 and invasive squamous cell carcinoma.
CONCLUSION
These observations suggest that carcinogenesis of invasive squamous cell carcinoma from CIN3 may be concerned with high risk HPV concentration and may be occurred via another pathway without HPV and p53 or p21 mutation.
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