Abstract/Details

The effects ofRB2/p130 on tumorigenesis


1998 1998

Other formats: Order a copy

Abstract (summary)

The retinoblastoma family of proteins, pRb/p105, p107 and pRb2/p130, are defined by their structural and functional homology to the patriarch of the family, Rb/p105, the prototypic tumor suppressor gene. Precise characterization of the proteins has revealed that even though the proteins may be able to functionally complement each another, they are not fully functionally redundant. The focus of the research presented herein has been the functional characterization of the putative tumor suppressor gene pRb2/p130 and its possible link to human cancer. Immunohistochemical studies were performed which demonstrated that lack of pRb2/p130 expression was an independent prognostic indicator that inversely correlated with the aggressiveness of human lung and endometrial cancers and could be used to identify patients at a five fold increased risk of dying from the disease. pRb2/p130 has been shown to be the target of several DNA tumor viruses that functionally inactivate the entire Rb-family to elicit neoplastic transformation. Evidence supporting the application of such a scenario to the development and/or progression of human cancer has been shown for mesothelioma. Furthermore, mutations have been detected in the RB2/p130 gene by southern blot analysis, SSCP and direct sequencing in human tumor cell lines and primary tumors. The cell cycle regulatory role and growth suppressive function of pRb2/p130 on tumor growth has been demonstrated in vitro and in vivo by development of an inducible expression system and by viral-mediated gene transfer. Additionally, the molecular mechanisms involved in the biological activity of pRb2/p130 have been examined. In conclusion, the "putative" tumor suppressor gene pRb2/p130 fulfills the definition of a tumor suppressor gene in that its expression is growth suppressive to tumor formation and the gene is found mutated in primary tumors. The direct role of pRb2/p130 in regulating the functional activity of the cell cycle machinery provides an additional link between neoplastic transformation and disruptions in the cell cycle machinery.

Indexing (details)


Subject
Genetics;
Oncology;
Molecular biology
Classification
0369: Genetics
0992: Oncology
0307: Molecular biology
Identifier / keyword
Health and environmental sciences; Biological sciences; P130; Tumorigenesis; pRb2/p130
Title
The effects ofRB2/p130 on tumorigenesis
Author
Howard-Claudio, Candace Michelle
Number of pages
467
Publication year
1998
Degree date
1998
School code
0272
Source
DAI-B 59/07, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780591961263, 0591961261
Advisor
Giordano, Antonio
University/institution
Thomas Jefferson University
University location
United States -- Pennsylvania
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
9841946
ProQuest document ID
304461068
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304461068
Access the complete full text

You can get the full text of this document if it is part of your institution's ProQuest subscription.

Try one of the following:

  • Connect to ProQuest through your library network and search for the document from there.
  • Request the document from your library.
  • Go to the ProQuest login page and enter a ProQuest or My Research username / password.