Human papillomavirus 18 oncoproteins E6 and E7 enhance irradiation- and chemotherapeutic agent-induced apoptosis in p53 and Rb mutated cervical cancer cell lines

Gokhan Kilic, M. Cardillo, M. Ozdemirli, B. Arun

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Tumor suppressor genes p53 and Rb are important in cell cycle control. Necessity of wild type p53 is implicated in irradiation-induced apoptosis. Numerous tumor cells carry p53 mutations and yet are sensitive to irradiation or chemotherapeutic agents. Therefore p53- and Rb-independent pathways must exist to account for irradiation-induced apoptosis. We evaluated the apoptotic response of a p53- and Rb-mutated, Human Papilloma Virus (HPV) negative cervical cancer cell line (C33a), and C33a cell Lines infected with HPV 18 oncoproteins E6, E7, and E6 and 7 using recombinant retrovirus to various apoptosis-inducing agents including gamma irradiation, mitomycin C (MMC), and staurosporine (SSP). Apoptosis was measured by avidinebiotin tunnel staining method. Our results showed significant apoptosis in C33a cell lines in response to gamma-irradiation, MMC, and SSP. Moreover, apoptosis was enhanced when HPV 18 E6, and E6 and 7 infected C33a cell lines were treated with irradiation, MMC, and SSP. HPV 18 E7 infected C33a cell lines enhanced the apoptotic response to irradiation and to MMC, but not to SP. In conclusion, our results imply the presence of a p53- and Rb-independent pathway in irradiation-induced apoptosis in cervical cancer cell lines: this effect is even more evident in HPV oncoprotein infected cell lines. The radiosensitizing effects of HPV oncoproteins may lead to new perspectives in the treatment of cervical cancer.

Original languageEnglish (US)
Pages (from-to)167-171
Number of pages5
JournalEuropean Journal of Gynaecological Oncology
Volume20
Issue number3
StatePublished - 1999
Externally publishedYes

Fingerprint

Papillomaviridae
Human papillomavirus 18
Oncogene Proteins
Uterine Cervical Neoplasms
Apoptosis
Cell Line
Mitomycin
Staurosporine
Stathmin
Radiation-Sensitizing Agents
Retroviridae
Cell Cycle Checkpoints
Tumor Suppressor Genes
Staining and Labeling
Mutation

Keywords

  • Apoptosis
  • C33a
  • HPV-7
  • HPV-E6
  • p53

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

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title = "Human papillomavirus 18 oncoproteins E6 and E7 enhance irradiation- and chemotherapeutic agent-induced apoptosis in p53 and Rb mutated cervical cancer cell lines",
abstract = "Tumor suppressor genes p53 and Rb are important in cell cycle control. Necessity of wild type p53 is implicated in irradiation-induced apoptosis. Numerous tumor cells carry p53 mutations and yet are sensitive to irradiation or chemotherapeutic agents. Therefore p53- and Rb-independent pathways must exist to account for irradiation-induced apoptosis. We evaluated the apoptotic response of a p53- and Rb-mutated, Human Papilloma Virus (HPV) negative cervical cancer cell line (C33a), and C33a cell Lines infected with HPV 18 oncoproteins E6, E7, and E6 and 7 using recombinant retrovirus to various apoptosis-inducing agents including gamma irradiation, mitomycin C (MMC), and staurosporine (SSP). Apoptosis was measured by avidinebiotin tunnel staining method. Our results showed significant apoptosis in C33a cell lines in response to gamma-irradiation, MMC, and SSP. Moreover, apoptosis was enhanced when HPV 18 E6, and E6 and 7 infected C33a cell lines were treated with irradiation, MMC, and SSP. HPV 18 E7 infected C33a cell lines enhanced the apoptotic response to irradiation and to MMC, but not to SP. In conclusion, our results imply the presence of a p53- and Rb-independent pathway in irradiation-induced apoptosis in cervical cancer cell lines: this effect is even more evident in HPV oncoprotein infected cell lines. The radiosensitizing effects of HPV oncoproteins may lead to new perspectives in the treatment of cervical cancer.",
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author = "Gokhan Kilic and M. Cardillo and M. Ozdemirli and B. Arun",
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T1 - Human papillomavirus 18 oncoproteins E6 and E7 enhance irradiation- and chemotherapeutic agent-induced apoptosis in p53 and Rb mutated cervical cancer cell lines

AU - Kilic, Gokhan

AU - Cardillo, M.

AU - Ozdemirli, M.

AU - Arun, B.

PY - 1999

Y1 - 1999

N2 - Tumor suppressor genes p53 and Rb are important in cell cycle control. Necessity of wild type p53 is implicated in irradiation-induced apoptosis. Numerous tumor cells carry p53 mutations and yet are sensitive to irradiation or chemotherapeutic agents. Therefore p53- and Rb-independent pathways must exist to account for irradiation-induced apoptosis. We evaluated the apoptotic response of a p53- and Rb-mutated, Human Papilloma Virus (HPV) negative cervical cancer cell line (C33a), and C33a cell Lines infected with HPV 18 oncoproteins E6, E7, and E6 and 7 using recombinant retrovirus to various apoptosis-inducing agents including gamma irradiation, mitomycin C (MMC), and staurosporine (SSP). Apoptosis was measured by avidinebiotin tunnel staining method. Our results showed significant apoptosis in C33a cell lines in response to gamma-irradiation, MMC, and SSP. Moreover, apoptosis was enhanced when HPV 18 E6, and E6 and 7 infected C33a cell lines were treated with irradiation, MMC, and SSP. HPV 18 E7 infected C33a cell lines enhanced the apoptotic response to irradiation and to MMC, but not to SP. In conclusion, our results imply the presence of a p53- and Rb-independent pathway in irradiation-induced apoptosis in cervical cancer cell lines: this effect is even more evident in HPV oncoprotein infected cell lines. The radiosensitizing effects of HPV oncoproteins may lead to new perspectives in the treatment of cervical cancer.

AB - Tumor suppressor genes p53 and Rb are important in cell cycle control. Necessity of wild type p53 is implicated in irradiation-induced apoptosis. Numerous tumor cells carry p53 mutations and yet are sensitive to irradiation or chemotherapeutic agents. Therefore p53- and Rb-independent pathways must exist to account for irradiation-induced apoptosis. We evaluated the apoptotic response of a p53- and Rb-mutated, Human Papilloma Virus (HPV) negative cervical cancer cell line (C33a), and C33a cell Lines infected with HPV 18 oncoproteins E6, E7, and E6 and 7 using recombinant retrovirus to various apoptosis-inducing agents including gamma irradiation, mitomycin C (MMC), and staurosporine (SSP). Apoptosis was measured by avidinebiotin tunnel staining method. Our results showed significant apoptosis in C33a cell lines in response to gamma-irradiation, MMC, and SSP. Moreover, apoptosis was enhanced when HPV 18 E6, and E6 and 7 infected C33a cell lines were treated with irradiation, MMC, and SSP. HPV 18 E7 infected C33a cell lines enhanced the apoptotic response to irradiation and to MMC, but not to SP. In conclusion, our results imply the presence of a p53- and Rb-independent pathway in irradiation-induced apoptosis in cervical cancer cell lines: this effect is even more evident in HPV oncoprotein infected cell lines. The radiosensitizing effects of HPV oncoproteins may lead to new perspectives in the treatment of cervical cancer.

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