Selection of human cervical epithelial cells that possess reduced apoptotic potential to low-oxygen conditions

Charlotte Y. Kim, Mitchell H. Tsai, Cynthia Osmanian, Thomas G. Graeber, Jong Eun Lee, Rona G. Giffard, Joseph A. DiPaolo, Donna M. Peehl, Amato J. Giaccia

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

Since human papillomavirus (HPV) infection is strongly associated with cervical neoplasia and tumor hypoxia has prognostic significance in human cervical carcinomas, we examined the relationship between hypoxia and apoptosis in human cervical epithelial cells expressing high-risk HPV type 16 oncoproteins. In vitro, hypoxia stimulated both p53 induction and apoptosis in primary cervical epithelial cells infected with the HPV E6 and E7 genes but not in cervical fibroblasts infected with E6 and E7. Furthermore, cell lines derived from HPV-associated human cervical squamous cell carcinomas were substantially less sensitive to apoptosis induced by hypoxia, indicating that these cell lines have acquired additional genetic alterations that reduced their apoptotic sensitivity. Although the process of long-term cell culturing resulted in selection for subpopulations of HPV oncoprotein- expressing cervical epithelial cells with diminished apoptotic potential, the exposure of cells to hypoxia greatly accelerated the selection process. These results provide evidence for the role of hypoxia-mediated selection of cells with diminished apoptotic potential in the progression of human tumors and can in part explain why cervical tumors that possess low pO2 values are more aggressive.

Original languageEnglish
Pages (from-to)4200-4204
Number of pages5
JournalCancer Research
Volume57
Issue number19
Publication statusPublished - 1997 Oct 1

Fingerprint

Epithelial Cells
Oxygen
Oncogene Proteins
Apoptosis
Cell Hypoxia
Cell Line
Neoplasms
Papillomavirus Infections
Human papillomavirus 16
Squamous Cell Carcinoma
Fibroblasts
Carcinoma
Hypoxia
Genes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kim, C. Y., Tsai, M. H., Osmanian, C., Graeber, T. G., Lee, J. E., Giffard, R. G., ... Giaccia, A. J. (1997). Selection of human cervical epithelial cells that possess reduced apoptotic potential to low-oxygen conditions. Cancer Research, 57(19), 4200-4204.
Kim, Charlotte Y. ; Tsai, Mitchell H. ; Osmanian, Cynthia ; Graeber, Thomas G. ; Lee, Jong Eun ; Giffard, Rona G. ; DiPaolo, Joseph A. ; Peehl, Donna M. ; Giaccia, Amato J. / Selection of human cervical epithelial cells that possess reduced apoptotic potential to low-oxygen conditions. In: Cancer Research. 1997 ; Vol. 57, No. 19. pp. 4200-4204.
@article{3504ab7e23924c9e98817a920f65d467,
title = "Selection of human cervical epithelial cells that possess reduced apoptotic potential to low-oxygen conditions",
abstract = "Since human papillomavirus (HPV) infection is strongly associated with cervical neoplasia and tumor hypoxia has prognostic significance in human cervical carcinomas, we examined the relationship between hypoxia and apoptosis in human cervical epithelial cells expressing high-risk HPV type 16 oncoproteins. In vitro, hypoxia stimulated both p53 induction and apoptosis in primary cervical epithelial cells infected with the HPV E6 and E7 genes but not in cervical fibroblasts infected with E6 and E7. Furthermore, cell lines derived from HPV-associated human cervical squamous cell carcinomas were substantially less sensitive to apoptosis induced by hypoxia, indicating that these cell lines have acquired additional genetic alterations that reduced their apoptotic sensitivity. Although the process of long-term cell culturing resulted in selection for subpopulations of HPV oncoprotein- expressing cervical epithelial cells with diminished apoptotic potential, the exposure of cells to hypoxia greatly accelerated the selection process. These results provide evidence for the role of hypoxia-mediated selection of cells with diminished apoptotic potential in the progression of human tumors and can in part explain why cervical tumors that possess low pO2 values are more aggressive.",
author = "Kim, {Charlotte Y.} and Tsai, {Mitchell H.} and Cynthia Osmanian and Graeber, {Thomas G.} and Lee, {Jong Eun} and Giffard, {Rona G.} and DiPaolo, {Joseph A.} and Peehl, {Donna M.} and Giaccia, {Amato J.}",
year = "1997",
month = "10",
day = "1",
language = "English",
volume = "57",
pages = "4200--4204",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "19",

}

Kim, CY, Tsai, MH, Osmanian, C, Graeber, TG, Lee, JE, Giffard, RG, DiPaolo, JA, Peehl, DM & Giaccia, AJ 1997, 'Selection of human cervical epithelial cells that possess reduced apoptotic potential to low-oxygen conditions', Cancer Research, vol. 57, no. 19, pp. 4200-4204.

Selection of human cervical epithelial cells that possess reduced apoptotic potential to low-oxygen conditions. / Kim, Charlotte Y.; Tsai, Mitchell H.; Osmanian, Cynthia; Graeber, Thomas G.; Lee, Jong Eun; Giffard, Rona G.; DiPaolo, Joseph A.; Peehl, Donna M.; Giaccia, Amato J.

In: Cancer Research, Vol. 57, No. 19, 01.10.1997, p. 4200-4204.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Selection of human cervical epithelial cells that possess reduced apoptotic potential to low-oxygen conditions

AU - Kim, Charlotte Y.

AU - Tsai, Mitchell H.

AU - Osmanian, Cynthia

AU - Graeber, Thomas G.

AU - Lee, Jong Eun

AU - Giffard, Rona G.

AU - DiPaolo, Joseph A.

AU - Peehl, Donna M.

AU - Giaccia, Amato J.

PY - 1997/10/1

Y1 - 1997/10/1

N2 - Since human papillomavirus (HPV) infection is strongly associated with cervical neoplasia and tumor hypoxia has prognostic significance in human cervical carcinomas, we examined the relationship between hypoxia and apoptosis in human cervical epithelial cells expressing high-risk HPV type 16 oncoproteins. In vitro, hypoxia stimulated both p53 induction and apoptosis in primary cervical epithelial cells infected with the HPV E6 and E7 genes but not in cervical fibroblasts infected with E6 and E7. Furthermore, cell lines derived from HPV-associated human cervical squamous cell carcinomas were substantially less sensitive to apoptosis induced by hypoxia, indicating that these cell lines have acquired additional genetic alterations that reduced their apoptotic sensitivity. Although the process of long-term cell culturing resulted in selection for subpopulations of HPV oncoprotein- expressing cervical epithelial cells with diminished apoptotic potential, the exposure of cells to hypoxia greatly accelerated the selection process. These results provide evidence for the role of hypoxia-mediated selection of cells with diminished apoptotic potential in the progression of human tumors and can in part explain why cervical tumors that possess low pO2 values are more aggressive.

AB - Since human papillomavirus (HPV) infection is strongly associated with cervical neoplasia and tumor hypoxia has prognostic significance in human cervical carcinomas, we examined the relationship between hypoxia and apoptosis in human cervical epithelial cells expressing high-risk HPV type 16 oncoproteins. In vitro, hypoxia stimulated both p53 induction and apoptosis in primary cervical epithelial cells infected with the HPV E6 and E7 genes but not in cervical fibroblasts infected with E6 and E7. Furthermore, cell lines derived from HPV-associated human cervical squamous cell carcinomas were substantially less sensitive to apoptosis induced by hypoxia, indicating that these cell lines have acquired additional genetic alterations that reduced their apoptotic sensitivity. Although the process of long-term cell culturing resulted in selection for subpopulations of HPV oncoprotein- expressing cervical epithelial cells with diminished apoptotic potential, the exposure of cells to hypoxia greatly accelerated the selection process. These results provide evidence for the role of hypoxia-mediated selection of cells with diminished apoptotic potential in the progression of human tumors and can in part explain why cervical tumors that possess low pO2 values are more aggressive.

UR - http://www.scopus.com/inward/record.url?scp=0030864485&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030864485&partnerID=8YFLogxK

M3 - Article

C2 - 9331075

AN - SCOPUS:0030864485

VL - 57

SP - 4200

EP - 4204

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 19

ER -

Kim CY, Tsai MH, Osmanian C, Graeber TG, Lee JE, Giffard RG et al. Selection of human cervical epithelial cells that possess reduced apoptotic potential to low-oxygen conditions. Cancer Research. 1997 Oct 1;57(19):4200-4204.