This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Carbone, M. Articles by Bocchetta, M. Search for Related Content PubMed PubMed Citation Articles by Carbone, M. Articles by Bocchetta, M.

A Novel Mechanism of Late Gene Silencing Drives SV40 Transformation of Human Mesothelial Cells

¹ Thoracic Oncology Program, Cancer Center of Hawaii and Department of Pathology, University of Hawaii Medical School, Honolulu, Hawaii; ² Human Genetics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania; and ³ Thoracic Oncology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, Illinois

Requests for reprints: Michele Carbone, University of Hawaii Medical School, 651 Ilalo Street, BSB-231-H, Honolulu, HI 96813. Phone: 808-440-4596; Fax: 808-587-0790; E-mail: mcarbone{at}crch.hawaii.edu.

Key Words: Carcinogenesis • DNA tumor viruses • SV40

Suppression of the late gene expression, usually by integration of the viral DNA into the host genome, is a critical step in DNA tumor virus carcinogenesis. SV40 induces high rates of transformation in infected primary human mesothelial cells in tissue culture, leading to the formation of immortal cell lines (SV40-transformed human mesothelial cell lines, S-HML). The studies described here were designed to elucidate the unusual susceptibility of primary human mesothelial cells to SV40 carcinogenesis. We found that S-HML contained wild-type, mostly episomal SV40 DNA. In these cells, the early genes that code for the viral oncogenes are expressed; at the same time, the synthesis of the late genes, capsid proteins, is suppressed and S-HML are not lysed. Late gene suppression is achieved through the production of antisense RNA molecules. These antisense RNA molecules originate in the early region of the SV40 circular chromosome and proceed in antisense orientation into the late gene region, leading to the formation of highly unstable double-strand RNA, which is rapidly degraded. Our results reveal a novel biological mechanism responsible for the suppression of late viral gene products, an important step in viral carcinogenesis in humans. [Cancer Res 2008;68(22):9488–96]