Linked Life Data

7926731

Source:http://linkedlifedata.com/resource/pubmed/id/7926731

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1994-11-17
pubmed:abstractText
Tumor suppressor proteins are believed to play a role in regulating cell cycle control during mammalian development. The E6 and E7 oncoproteins from human papillomavirus type 16 are known to affect cell growth control, at least in part, through their inactivation of cellular tumor suppressor gene products, p53 and Rb, respectively. Therefore, these viral proteins can serve as trans-dominant repressors of tumor suppressor gene function. To study the potential role of p53 and Rb in murine lens morphogenesis, we generated transgenic mice in which the expression of E6 or E7 was directed to the developing lens. Transgenic mice expressing E7 exhibited microphthalmia and cataracts, whereas transgenic mice expressing E6 exhibited cataracts without noticeable microphthalmia. Microscopic analysis of the lenses from neonatal and adult E7 transgenic mice revealed inhibition of lens fiber cell differentiation, induction of cell proliferation in spatially inappropriate regions of the lens, and apoptosis. Transgenic mice expressing a mutant E7 that is defective in Rb/p107 binding exhibited normal eyes, suggesting that the activity of Rb and/or Rb-like proteins is required for the perturbation of lens development and induction of apoptosis in E7 mice. Microscopic analysis of lenses from E6 neonatal and adult transgenic mice indicated the presence of nuclei in elongated fiber cells, suggesting that E6 inhibits lens fiber cell denucleation. Furthermore, expression of E6 inhibited the apoptotic-like DNA degradation observed in the lenses of nontransgenic 15.5-day embryos. In lenses from neonatal E6 x E7 double transgenic mice, the level of apoptosis was reduced compared with that seen in lenses from neonatal E7 mice. In adults E6 x E7 double transgenic mice, lens tumors developed, whereas in E6 or E7 only transgenic mice, tumors did not. Taken together, these results point to specific roles in lens morphogenesis for Rb and p53 and to the necessity of these tumor suppressor gene products in regulating exit from the normal cell division cycle in differentiating lens fiber cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0890-9369
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1285-99
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:7926731-Animals, pubmed-meshheading:7926731-Apoptosis, pubmed-meshheading:7926731-Base Sequence, pubmed-meshheading:7926731-Cell Differentiation, pubmed-meshheading:7926731-DNA, pubmed-meshheading:7926731-Genes, Tumor Suppressor, pubmed-meshheading:7926731-Lens, Crystalline, pubmed-meshheading:7926731-Mice, pubmed-meshheading:7926731-Mice, Transgenic, pubmed-meshheading:7926731-Molecular Sequence Data, pubmed-meshheading:7926731-Oncogene Proteins, Viral, pubmed-meshheading:7926731-Papillomaviridae, pubmed-meshheading:7926731-Papillomavirus E7 Proteins, pubmed-meshheading:7926731-Polymerase Chain Reaction, pubmed-meshheading:7926731-Protein Binding, pubmed-meshheading:7926731-RNA, Messenger, pubmed-meshheading:7926731-Repressor Proteins, pubmed-meshheading:7926731-Retinoblastoma Protein, pubmed-meshheading:7926731-Structure-Activity Relationship, pubmed-meshheading:7926731-Tumor Suppressor Protein p53
pubmed:year
1994
pubmed:articleTitle
Altered cell cycle regulation in the lens of HPV-16 E6 or E7 transgenic mice: implications for tumor suppressor gene function in development.
pubmed:affiliation
Department of Anatomy, University of Wisconsin Medical School, Madison 53706.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't