Abstract

The overall goal of this project is to identify changes in cellular gene expression which cooperate with HPV in the progression of HPV immortalized cells to malignancy. The steps in the conversion of human epithelial cells to tumorigenicity will be studied. Cofactors identified as important in epidemiology projects of this program will be examined in transformation and tumor induction assays for effects on cells expressing HPV genes and for direct effects on viral gene expression. cDNA libraries will be constructed from immortalized, transformed and tumor cells and differentially expressed genes identified by subtractive hybridization. Human tumor tissue will be screened using probes derived from these experiments. The development and significance of chromosomal changes will be examined by cytogenetic analysis to develop an understanding of the genetic instability found in HPV-immortalized cells.
One aim of this analysis will be to identify loci of tumor suppressor genes involved in HPV-associated tumor cells. The factors contributing to the blocks in terminal differentiation in HPV immortalized cells will be examined in the organotypic cell culture system.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA042792-06A1
Application #
3795418
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109

  Publications

Bao, Xiao; Hanson, Aimee L; Madeleine, Margaret M et al. (2018) HLA and KIR Associations of Cervical Neoplasia. J Infect Dis 218:2006-2015
Leo, Paul J; Madeleine, Margaret M; Wang, Sophia et al. (2017) Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study. PLoS Genet 13:e1006866
Wallace, Nicholas A; Khanal, Sujita; Robinson, Kristin L et al. (2017) High-Risk Alphapapillomavirus Oncogenes Impair the Homologous Recombination Pathway. J Virol 91:
Madeleine, Margaret M; Johnson, Lisa G; Doody, David R et al. (2016) Natural Antibodies to Human Papillomavirus 16 and Recurrence of Vulvar High-Grade Intraepithelial Neoplasia (VIN3). J Low Genit Tract Dis 20:257-60
Hardikar, Sheetal; Johnson, Lisa G; Malkki, Mari et al. (2015) A population-based case-control study of genetic variation in cytokine genes associated with risk of cervical and vulvar cancers. Gynecol Oncol 139:90-6
Wallace, Nicholas A; Robinson, Kristin; Howie, Heather L et al. (2015) ?-HPV 5 and 8 E6 disrupt homology dependent double strand break repair by attenuating BRCA1 and BRCA2 expression and foci formation. PLoS Pathog 11:e1004687
Galloway, Denise A; Laimins, Laimonis A (2015) Human papillomaviruses: shared and distinct pathways for pathogenesis. Curr Opin Virol 14:87-92
Safaeian, Mahboobeh; Johnson, Lisa G; Yu, Kai et al. (2014) Human Leukocyte Antigen Class I and II Alleles and Cervical Adenocarcinoma. Front Oncol 4:119
Madeleine, Margaret M; Carter, Joseph J; Johnson, Lisa G et al. (2014) Risk of squamous cell skin cancer after organ transplant associated with antibodies to cutaneous papillomaviruses, polyomaviruses, and TMC6/8 (EVER1/2) variants. Cancer Med 3:1440-7
Wallace, Nicholas A; Galloway, Denise A (2014) Manipulation of cellular DNA damage repair machinery facilitates propagation of human papillomaviruses. Semin Cancer Biol 26:30-42

Showing the most recent 10 out of 127 publications