Linked Life Data

14985467

Source:http://linkedlifedata.com/resource/pubmed/id/14985467

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-2-26
pubmed:abstractText
Many defects in cancer cells are in molecules regulating G(1)-phase cyclin-dependent kinases (cdks), which are responsible for modulating the activities of Rb family growth-suppressing proteins. Models for understanding how such defects affect proliferation assume that cdks are responsible for sequentially phosphorylating, and hence inactivating, the growth-suppressing functions of Rb family proteins, thus promoting cell cycle progression. However, cdks also play a role in formation of growth-suppressing forms of pRb family molecules, including the "hypophosphorylated" species of pRb itself. Here, it is shown that normal human mammary epithelial cells have a high amount of cdk6 protein and activity, but all breast tumor-derived cell lines analyzed had reduced levels, with several having little or no cdk6. Immunohistochemical studies showed reduced levels of cdk6 in breast tumor cells as compared with normal breast tissue in vivo. Cdk6 levels in two breast tumor cell lines were restored to those characteristic of normal human mammary epithelial cells by DNA transfection. The cells had a reduced growth rate compared with parental tumor cells; cells that lost ectopic expression of cdk6 reverted to the faster growth rate of parental cells. Cell lines with restored cdk6 levels accumulated higher amounts of the Rb family protein p130 as well as E2F4, a suppressing member of the E2F family of transcription factors, in their nuclei. The results suggest that cdk6 restrains rather than stimulates breast epithelial cell proliferation and that its loss or down-regulation could play a role in breast tumor development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1541-7786
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
105-14
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Cyclin-dependent kinase 6 inhibits proliferation of human mammary epithelial cells.
pubmed:affiliation
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA. lucasj@njc.org
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't