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Genetic requirements for the transfo...

Seger, Yvette Renee.

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Genetic requirements for the transformation of normal human cells.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Genetic requirements for the transformation of normal human cells./
Author:	Seger, Yvette Renee.
Description:	246 p.
Notes:	Source: Dissertation Abstracts International, Volume: 65-04, Section: B, page: 1664.
Contained By:	Dissertation Abstracts International65-04B.
Subject:	Biology, Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3131274
ISBN:	0496785168

Genetic requirements for the transformation of normal human cells.
Seger, Yvette Renee.

Genetic requirements for the transformation of normal human cells. - 246 p.

Source: Dissertation Abstracts International, Volume: 65-04, Section: B, page: 1664.

Thesis (Ph.D.)--State University of New York at Stony Brook, 2004.

Our knowledge of the transformation process has emerged largely from studies of primary rodent cells and animal models. In primary rodent fibroblasts, the transformation process is well-defined and usually requires two genetic alterations. However, rodent transformation models do not perfectly recapitulate the transformation process in humans as it is impossible to transform normal human cells into tumor cells using the same oncogene combinations that are effective in rodent cells. One obvious difference between rodent and human cell models is the requirement for telomerase, the enzyme responsible for maintaining telomeres. In rodent cells, transformation is independent of exogenous telomerase induction due to promiscuous telomerase expression and constitutively long telomeres. The potential importance of telomerase in human transformation processes has been supported by the fact that a majority of human tumors are telomerase-positive.{09}In addition, previous reports have indicated that the direct expression of the telomerase catalytic subunit hTERT is a vital component of the human cell transformation equation.

ISBN: 0496785168Subjects--Topical Terms:

1017730
Biology, Genetics.

Genetic requirements for the transformation of normal human cells.
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100 1 $a Seger, Yvette Renee. $3 1935471
245 1 0 $a Genetic requirements for the transformation of normal human cells.
300 $a 246 p.
500 $a Source: Dissertation Abstracts International, Volume: 65-04, Section: B, page: 1664.
500 $a Adviser: Gregory J. Hannon.
502 $a Thesis (Ph.D.)--State University of New York at Stony Brook, 2004.
520 $a Our knowledge of the transformation process has emerged largely from studies of primary rodent cells and animal models. In primary rodent fibroblasts, the transformation process is well-defined and usually requires two genetic alterations. However, rodent transformation models do not perfectly recapitulate the transformation process in humans as it is impossible to transform normal human cells into tumor cells using the same oncogene combinations that are effective in rodent cells. One obvious difference between rodent and human cell models is the requirement for telomerase, the enzyme responsible for maintaining telomeres. In rodent cells, transformation is independent of exogenous telomerase induction due to promiscuous telomerase expression and constitutively long telomeres. The potential importance of telomerase in human transformation processes has been supported by the fact that a majority of human tumors are telomerase-positive.{09}In addition, previous reports have indicated that the direct expression of the telomerase catalytic subunit hTERT is a vital component of the human cell transformation equation.
520 $a In this thesis, I have developed a human cell transformation system that is independent of direct induction of hTERT or a gene previously shown to be capable of activating telomerase. I have shown that the combined expression of adenovirus E1A, Ha-RasV12 and MDM2 (ERM) is sufficient for the conversion of a normal human cell into a cancer cell. Notably, these cells are telomerase negative upon injection into nude mice, and the resultant tumors are also negative for telomerase activity. As a result, we see continuous telomere shortening and chromosomal abnormalities similar to those seen in telomerase-null mice. This suggests that alterations in telomere biology must be viewed similarly to genomic instability as catalysts of transformation rather than central components of the transformed phenotype.
520 $a This ERM transformation model is now functioning as a highly tractable system within which several RNA interference (RNAi)-based approaches can be applied. Most notably, we are currently utilizing stably expressed short-hairpin RNA constructs to knockdown expression of E1A targets in order to rescue functional deletion mutants of E1A and restore transforming function. Similarly, a hairpin rescue screen could eventually identify additional genes whose silencing contributes to E1A-mediated transformation.
590 $a School code: 0771.
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Biology, Molecular. $3 1017719
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773 0 $t Dissertation Abstracts International $g 65-04B.
790 1 0 $a Hannon, Gregory J., $e advisor
790 $a 0771
791 $a Ph.D.
792 $a 2004
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3131274