Linked Life Data

8782662

Source:http://linkedlifedata.com/resource/pubmed/id/8782662

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1996-10-24
pubmed:abstractText
We examined the effects of the introduction of H-ras oncogene into murine cell line NIH3T3 on growth inhibition by topoisomerase-I (topo-I) inhibitors. The H-ras-transformed cells (pT22-3) showed approximately 12-fold increased sensitivity to a novel topo-I inhibitor, NB-506 [6-N-formylamino-12,13-dihydro-1,11-dihydroxy-13-(beta-D-glucopyranosyl) -5H-indolo(2,3-a)pyrrolo(3,4-c) carbazole-5,7(6H)-dione], compared with the parental NIH3T3 cells. pT22-3 also showed increased sensitivity to other topo-I inhibitors such as camptothecin (approx. 3.0-fold) and CPT-11 (irinotecan, approx. 3.0-fold). Transformation of NIH3T3 by another oncogene (erbB2) did not affect their sensitivity to these topo-I inhibitors. pT22-3 had approximately 32-fold higher topo-I activity than NIH3T3, but the same topo-I content. In a cell-free system, topo-I activity was increased 2-fold by addition of the H-ras protein precipitated from pT22-3 cells. Topo I in the nuclear extract of pT22-3 was eluted easily by low concentrations of NaCl compared with that of NIH3T3, suggesting a qualitative change in pT22-3 topo 1. Increased phosphorylation of topo I was observed in pT22-3. Furthermore, NB-506 decreased the amount of the GTP-bound form of the H-ras product in pT22-3 cells. These results suggest that the high growth-inhibitory effect of a topo-I inhibitor, NB-506, on H-ras-transformed NIH3T3 cells is due to the H-ras-mediated signal-transduction pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
702-8
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Hypersensitivity of NIH3T3 cells transformed by H-ras gene to DNA-topoisomerase-I inhibitors.
pubmed:affiliation
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't