TY - JOUR
T1 - Clonal selection for transcriptionally active viral oncogenes during progression to cancer
AU - Van Tine, Brian A.
AU - Kappes, John C.
AU - Banerjee, N. Sanjib
AU - Knops, Judith
AU - Lai, Lilin
AU - Steenbergen, Renske D.M.
AU - Meijer, Chris L.J.M.
AU - Snijders, Peter J.F.
AU - Chatis, Pamela
AU - Broker, Thomas R.
AU - Moen, Phillip T.
AU - Chow, Louise T.
PY - 2004/10
Y1 - 2004/10
N2 - Primary keratinocytes immortalized by human papillomaviruses (HPVs), along with HPV-induced cervical carcinoma cell lines, are excellent models for investigating neoplastic progression to cancer. By simultaneously visualizing viral DNA and nascent viral transcripts in interphase nuclei, we demonstrated for the first time a selection for a single dominant papillomavirus transcription center or domain (PVTD) independent of integrated viral DNA copy numbers or loci. The PVTD did not associate with several known subnuclear addresses but was almost always perinucleolar. Silent copies of the viral genome were activated by growth in the DNA methylation inhibitor 5-azacytidine. HPV-immortalized keratinocytes supertransduced with HPV oncogenes and selected for marker gene coexpression underwent crisis, and the surviving cells transcribed only the newly introduced genes. Thus, transcriptional selection in response to environmental changes is a dynamic process to achieve optimal gene expression for cell survival. This phenomenon may be critical in clonal selection during carcinogenesis. Examination of HPV-associated cancers supports this hypothesis.
AB - Primary keratinocytes immortalized by human papillomaviruses (HPVs), along with HPV-induced cervical carcinoma cell lines, are excellent models for investigating neoplastic progression to cancer. By simultaneously visualizing viral DNA and nascent viral transcripts in interphase nuclei, we demonstrated for the first time a selection for a single dominant papillomavirus transcription center or domain (PVTD) independent of integrated viral DNA copy numbers or loci. The PVTD did not associate with several known subnuclear addresses but was almost always perinucleolar. Silent copies of the viral genome were activated by growth in the DNA methylation inhibitor 5-azacytidine. HPV-immortalized keratinocytes supertransduced with HPV oncogenes and selected for marker gene coexpression underwent crisis, and the surviving cells transcribed only the newly introduced genes. Thus, transcriptional selection in response to environmental changes is a dynamic process to achieve optimal gene expression for cell survival. This phenomenon may be critical in clonal selection during carcinogenesis. Examination of HPV-associated cancers supports this hypothesis.
UR - http://www.scopus.com/inward/record.url?scp=4644332773&partnerID=8YFLogxK
U2 - 10.1128/JVI.78.20.11172-11186.2004
DO - 10.1128/JVI.78.20.11172-11186.2004
M3 - Article
C2 - 15452237
AN - SCOPUS:4644332773
SN - 0022-538X
VL - 78
SP - 11172
EP - 11186
JO - Journal of virology
JF - Journal of virology
IS - 20
ER -