Enhanced expression of anti-apoptotic proteins in human papillomavirus- immortalized and cigarette smoke condensate-transformed human endocervical cells: Correlation with resistance to apoptosis induced by DNA damage

Xiaolong Yang, Yawei Hao, Mary M. Pater, Shou Ching Tang, Alan Pater

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Apoptosis plays an important role in various biological processes including embryogenesis, differentiation, homeostasis, and oncogenesis. We have developed a system composed of primary human endocervical cells (HEN), HEN immortalized by human papillomavirus (HPV) type 16, and their counterparts subsequently malignantly transformed by cigarette smoke condensate (CSC). To understand the role of apoptosis in the multistep oncogenesis of human cervical cells, we examined the expression of apoptosis- associated proteins in our in vitro model system. The results showed no significant difference in the levels of apoptosis-inducing proteins bak and bax among all the cell types examined. On the other hand, the levels of apoptosis-inhibiting proteins bcl-2, bcl-x(L) and BAG-1 increased progressively after immortalization and transformation. The p53 protein level decreased in the HPV16-immortalized HEN and increased in one of two lines of the CSC-transformed HEN. Further, the increased levels of apoptosis- inhibiting proteins in the HPV16-immortalized and the CSC-transformed HEN correlated with progressively increased resistance of these cells to apoptosis induced by staurosporine or cisplatin. This study provided the first evidence that overexpression of apoptosis-inhibiting proteins is important for both multistep oncogenesis and resistance of human endocervical cells to apoptosis induced by DNA-damaging reagents.

Original languageEnglish (US)
Pages (from-to)95-101
Number of pages7
JournalMolecular Carcinogenesis
Volume22
Issue number2
DOIs
StatePublished - Jun 1 1998

Keywords

  • Apoptosis
  • Cervix
  • Cigarette smoke
  • DNA damage
  • Human papillomavirus
  • Multistage oncogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'Enhanced expression of anti-apoptotic proteins in human papillomavirus- immortalized and cigarette smoke condensate-transformed human endocervical cells: Correlation with resistance to apoptosis induced by DNA damage'. Together they form a unique fingerprint.

  • Cite this