NDLI: Role of SV40 Integration Site at Chromosomal Interval 1q21.1 in Immortalized CRL2504 Cells

Content Provider	PubMed Central
Author	Liu, Jinglan Kaur, Gurpreet Zhawar, Vikramjit K. Zimonjic, Drazen B. Popescu, Nicholas C. Kandpal, Raj P. Athwal, Raghbir S.
Abstract	We have applied a functional gene transfer strategy to demonstrate the importance of viral integration site in cellular immortalization. The large tumor antigen of SV40 is capable of extending the cellular life span by sequestering tumor suppressor proteins pRB and p53 in virus-transformed human cells. Although SV40-LT is essential, it is not sufficient for cellular immortalization, suggesting that additional alterations in cellular genes are required to attain infinite proliferation. We demonstrate here that the disruption of human chromosomal interval at 1q21.1, by SV40 integration, can be an essential step for cellular immortalization. The transfer of a 150Kb bacterial artificial chromosome (BAC) clone, RP364B14, corresponding to viral integration site in CRL2504 cells, reverted their immortal phenotype. Interestingly, the BAC transfer clones of CRL-2504 cells displayed characteristics of either senescence as shown by β-galactosidase activity or apoptosis as revealed by positive staining with M30 cytoDeath antibody. The SV40 integration at 1q21.1, in the vicinity of epidermal differentiation complex genes, resulted in the down-regulation of the filaggrin (FLG) gene that is part of the epidermal differentiation complex. FLG gene expression was restored to its normal levels in BAC transfer senescent and apoptotic clones. Our results suggest that the disruption of native genomic sequence by SV40 may alter expression of genes involved in senescence and apoptosis by modulating chromatin structure. These studies imply that identification of genes located in the vicinity of viral integration sites in human cancers may be helpful in developing new diagnostic and therapeutic strategies.
Related Links	http://dx.doi.org/10.1158/0008-5472.can-09-1003
Ending Page	7825
Page Count	7
Starting Page	7819
File Format	PDF
ISSN	00085472
e-ISSN	15387445
Journal	Cancer research
Issue Number	19
Volume Number	69
Language	English
Publisher Date	2009-10-01
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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Role of SV40 Integration Site at Chromosomal Interval 1q21.1 in Immortalized CRL2504 Cells

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