Human papillomavirus 16/18 E6 oncoprotein is expressed in lung cancer and related with p53 inactivation

Ya Wen Cheng, Ming Fang Wu, John Wang, Kun Tu Yeh, Yih Gang Goan, Hui Ling Chiou, Chih Yi Chen, Huei Lee

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Inactivation of p53 by human papillomavirus 16/18 E6 plays a crucial role in cervical tumorigenesis. To investigate the involvement of HPV16/18 in lung tumorigenesis, the association between HPV16 or HPV18 E6 and p53 protein expression in 122 lung tumors was evaluated by immunohistochemistry, and data showed that HPV16/18 E6 expression correlated inversely with p53 expression, which was further confirmed by tissue in situ immunostaining. Real-time reverse transcription-PCR analysis indicated that E6-positive tumors had lower p21 WAF1/CIP1 and mdm2 mRNA levels than E6-negative tumors. To elucidate the role of E6 in p53 inactivation, we successfully established lung adenocarcinoma cell lines with or without HPV16 infection from patients' pleural effusions. Western blotting showed that E6 protein was indeed expressed in HPV16-infected cells and a lower level of p53 protein was observed in E6-positive cells compared with E6-negative cells. Moreover, the levels of p21WAF1/CIP1 and mdm2 mRNA in E6-positive cells were lower than in E6-negative cells. The interaction of E6 with p53 protein was revealed by immunoprecipitation assay showing that p53 could be inactivated by E6 protein. Conversely, p53 proteins and p21WAF1/CIP1 and mdm2 mRNA expressions were restored in E6-knockdown cells by RNA interference compared with control cells. These results reveal that HPV16/18 E6 may be partially involved in p53 inactivation to down-regulate p21WAF1/CIP1 and mdm2 transcription. In conclusion, HPV16/18 E6 is indeed expressed in HPV DNA-positive lung tumors and is involved in p53 inactivation to contributing to HPV-mediated lung tumorigenesis.

Original languageEnglish
Pages (from-to)10686-10693
Number of pages8
JournalCancer Research
Volume67
Issue number22
DOIs
Publication statusPublished - Nov 15 2007
Externally publishedYes

Fingerprint

Human papillomavirus 18
Human papillomavirus 16
Oncogene Proteins
Lung Neoplasms
Lung
Carcinogenesis
Proteins
Messenger RNA
Neoplasms
Pleural Effusion
RNA Interference
Immunoprecipitation
Reverse Transcription
Down-Regulation
Western Blotting
Immunohistochemistry
Cell Line
Polymerase Chain Reaction
DNA
Infection

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cheng, Y. W., Wu, M. F., Wang, J., Yeh, K. T., Goan, Y. G., Chiou, H. L., ... Lee, H. (2007). Human papillomavirus 16/18 E6 oncoprotein is expressed in lung cancer and related with p53 inactivation. Cancer Research, 67(22), 10686-10693. https://doi.org/10.1158/0008-5472.CAN-07-1461

Human papillomavirus 16/18 E6 oncoprotein is expressed in lung cancer and related with p53 inactivation. / Cheng, Ya Wen; Wu, Ming Fang; Wang, John; Yeh, Kun Tu; Goan, Yih Gang; Chiou, Hui Ling; Chen, Chih Yi; Lee, Huei.

In: Cancer Research, Vol. 67, No. 22, 15.11.2007, p. 10686-10693.

Research output: Contribution to journalArticle

Cheng, YW, Wu, MF, Wang, J, Yeh, KT, Goan, YG, Chiou, HL, Chen, CY & Lee, H 2007, 'Human papillomavirus 16/18 E6 oncoprotein is expressed in lung cancer and related with p53 inactivation', Cancer Research, vol. 67, no. 22, pp. 10686-10693. https://doi.org/10.1158/0008-5472.CAN-07-1461
Cheng, Ya Wen ; Wu, Ming Fang ; Wang, John ; Yeh, Kun Tu ; Goan, Yih Gang ; Chiou, Hui Ling ; Chen, Chih Yi ; Lee, Huei. / Human papillomavirus 16/18 E6 oncoprotein is expressed in lung cancer and related with p53 inactivation. In: Cancer Research. 2007 ; Vol. 67, No. 22. pp. 10686-10693.
@article{ccd4f29ea5294eb19bcd0dc0ccf67b01,
title = "Human papillomavirus 16/18 E6 oncoprotein is expressed in lung cancer and related with p53 inactivation",
abstract = "Inactivation of p53 by human papillomavirus 16/18 E6 plays a crucial role in cervical tumorigenesis. To investigate the involvement of HPV16/18 in lung tumorigenesis, the association between HPV16 or HPV18 E6 and p53 protein expression in 122 lung tumors was evaluated by immunohistochemistry, and data showed that HPV16/18 E6 expression correlated inversely with p53 expression, which was further confirmed by tissue in situ immunostaining. Real-time reverse transcription-PCR analysis indicated that E6-positive tumors had lower p21 WAF1/CIP1 and mdm2 mRNA levels than E6-negative tumors. To elucidate the role of E6 in p53 inactivation, we successfully established lung adenocarcinoma cell lines with or without HPV16 infection from patients' pleural effusions. Western blotting showed that E6 protein was indeed expressed in HPV16-infected cells and a lower level of p53 protein was observed in E6-positive cells compared with E6-negative cells. Moreover, the levels of p21WAF1/CIP1 and mdm2 mRNA in E6-positive cells were lower than in E6-negative cells. The interaction of E6 with p53 protein was revealed by immunoprecipitation assay showing that p53 could be inactivated by E6 protein. Conversely, p53 proteins and p21WAF1/CIP1 and mdm2 mRNA expressions were restored in E6-knockdown cells by RNA interference compared with control cells. These results reveal that HPV16/18 E6 may be partially involved in p53 inactivation to down-regulate p21WAF1/CIP1 and mdm2 transcription. In conclusion, HPV16/18 E6 is indeed expressed in HPV DNA-positive lung tumors and is involved in p53 inactivation to contributing to HPV-mediated lung tumorigenesis.",
author = "Cheng, {Ya Wen} and Wu, {Ming Fang} and John Wang and Yeh, {Kun Tu} and Goan, {Yih Gang} and Chiou, {Hui Ling} and Chen, {Chih Yi} and Huei Lee",
year = "2007",
month = "11",
day = "15",
doi = "10.1158/0008-5472.CAN-07-1461",
language = "English",
volume = "67",
pages = "10686--10693",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "22",

}

TY - JOUR

T1 - Human papillomavirus 16/18 E6 oncoprotein is expressed in lung cancer and related with p53 inactivation

AU - Cheng, Ya Wen

AU - Wu, Ming Fang

AU - Wang, John

AU - Yeh, Kun Tu

AU - Goan, Yih Gang

AU - Chiou, Hui Ling

AU - Chen, Chih Yi

AU - Lee, Huei

PY - 2007/11/15

Y1 - 2007/11/15

N2 - Inactivation of p53 by human papillomavirus 16/18 E6 plays a crucial role in cervical tumorigenesis. To investigate the involvement of HPV16/18 in lung tumorigenesis, the association between HPV16 or HPV18 E6 and p53 protein expression in 122 lung tumors was evaluated by immunohistochemistry, and data showed that HPV16/18 E6 expression correlated inversely with p53 expression, which was further confirmed by tissue in situ immunostaining. Real-time reverse transcription-PCR analysis indicated that E6-positive tumors had lower p21 WAF1/CIP1 and mdm2 mRNA levels than E6-negative tumors. To elucidate the role of E6 in p53 inactivation, we successfully established lung adenocarcinoma cell lines with or without HPV16 infection from patients' pleural effusions. Western blotting showed that E6 protein was indeed expressed in HPV16-infected cells and a lower level of p53 protein was observed in E6-positive cells compared with E6-negative cells. Moreover, the levels of p21WAF1/CIP1 and mdm2 mRNA in E6-positive cells were lower than in E6-negative cells. The interaction of E6 with p53 protein was revealed by immunoprecipitation assay showing that p53 could be inactivated by E6 protein. Conversely, p53 proteins and p21WAF1/CIP1 and mdm2 mRNA expressions were restored in E6-knockdown cells by RNA interference compared with control cells. These results reveal that HPV16/18 E6 may be partially involved in p53 inactivation to down-regulate p21WAF1/CIP1 and mdm2 transcription. In conclusion, HPV16/18 E6 is indeed expressed in HPV DNA-positive lung tumors and is involved in p53 inactivation to contributing to HPV-mediated lung tumorigenesis.

AB - Inactivation of p53 by human papillomavirus 16/18 E6 plays a crucial role in cervical tumorigenesis. To investigate the involvement of HPV16/18 in lung tumorigenesis, the association between HPV16 or HPV18 E6 and p53 protein expression in 122 lung tumors was evaluated by immunohistochemistry, and data showed that HPV16/18 E6 expression correlated inversely with p53 expression, which was further confirmed by tissue in situ immunostaining. Real-time reverse transcription-PCR analysis indicated that E6-positive tumors had lower p21 WAF1/CIP1 and mdm2 mRNA levels than E6-negative tumors. To elucidate the role of E6 in p53 inactivation, we successfully established lung adenocarcinoma cell lines with or without HPV16 infection from patients' pleural effusions. Western blotting showed that E6 protein was indeed expressed in HPV16-infected cells and a lower level of p53 protein was observed in E6-positive cells compared with E6-negative cells. Moreover, the levels of p21WAF1/CIP1 and mdm2 mRNA in E6-positive cells were lower than in E6-negative cells. The interaction of E6 with p53 protein was revealed by immunoprecipitation assay showing that p53 could be inactivated by E6 protein. Conversely, p53 proteins and p21WAF1/CIP1 and mdm2 mRNA expressions were restored in E6-knockdown cells by RNA interference compared with control cells. These results reveal that HPV16/18 E6 may be partially involved in p53 inactivation to down-regulate p21WAF1/CIP1 and mdm2 transcription. In conclusion, HPV16/18 E6 is indeed expressed in HPV DNA-positive lung tumors and is involved in p53 inactivation to contributing to HPV-mediated lung tumorigenesis.

UR - http://www.scopus.com/inward/record.url?scp=36348994476&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36348994476&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-07-1461

DO - 10.1158/0008-5472.CAN-07-1461

M3 - Article

C2 - 18006810

AN - SCOPUS:36348994476

VL - 67

SP - 10686

EP - 10693

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 22

ER -