Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
1995-8-10
pubmed:abstractText
Although tyrosine kinases (Tyr-k) are known to play a role in regulating proliferation of normal, preneoplastic and neoplastic cells, little is known about the identity of different species of Tyr-k involved in this process. Utilizing a non-denaturing polyacrylamide gel electrophoresis system, in which the separated proteins from tissue extracts are assayed directly for Tyr-k, we attempted to identify the species of Tyr-k that may be involved in azoxymethane (AOM) induction of colonic mucosal ornithine decarboxylase (ODC) activity, an enzyme whose activity is known to rise in rapidly proliferating cells. We have observed that 5 days after a single injection of the colonic carcinogen AOM (20 mg/kg body wt) to 3-4-month old rats, a significant 230% rise in colonic mucosal proliferative activity (as evidenced by 5-bromo-2'-deoxyuridine (BrdU) immunoreactivity) was also accompanied by a 550% increase in ODC activity. This was also associated with a marked rise (140-240%) in the relative activity of Tyr-k of three mucosal proteins with MI of 165, 145 and 125 kDa. Since the molecular mass of one of the Tyr-k (165 kDa) corresponded to that of EGF-receptor (EGF-R), this led us to examine the role of EGF-R Tyr-k in AOM induction of colonic mucosal ODC. We observed that a 320% increase in mucosal ODC activity, 5 days after AOM injection, was accompanied by over 200% rise in Tyr-k activity of EGF-R. Daily injection of tyrphostin (300 micrograms/kg body wt.), a Tyr-k inhibitor with a higher specificity for EGF-R Tyr-k, significantly attenuated AOM-induced stimulation of both ODC and Tyr-k activity of EGF-R. Administration of AOM also stimulated the rate of synthesis and secretion of TGF-alpha in isolated colonocytes. In addition, the levels of TGF-alpha and its mRNA in the colonic mucosa were also found to be 100% and 250% higher, respectively, in AOM-treated rats when compared with the controls. We suggest that (a) activation of intrinsic Tyr-k of EGF-R is an important event in AOM induction of colonic mucosal proliferative processes, and (b) this activation is thought to be mediated by TGF-alpha through an autocrine mechanism.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Azoxymethane, http://linkedlifedata.com/resource/pubmed/chemical/Bromodeoxyuridine, http://linkedlifedata.com/resource/pubmed/chemical/Catechols, http://linkedlifedata.com/resource/pubmed/chemical/Nitriles, http://linkedlifedata.com/resource/pubmed/chemical/Ornithine Decarboxylase, http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor alpha, http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine, http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins, http://linkedlifedata.com/resource/pubmed/chemical/tyrphostin 47
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
1244
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
368-76
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:7541245-Animals, pubmed-meshheading:7541245-Azoxymethane, pubmed-meshheading:7541245-Bromodeoxyuridine, pubmed-meshheading:7541245-Catechols, pubmed-meshheading:7541245-Cell Division, pubmed-meshheading:7541245-Colon, pubmed-meshheading:7541245-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:7541245-Enzyme Induction, pubmed-meshheading:7541245-Immunosorbent Techniques, pubmed-meshheading:7541245-Intestinal Mucosa, pubmed-meshheading:7541245-Kinetics, pubmed-meshheading:7541245-Molecular Weight, pubmed-meshheading:7541245-Nitriles, pubmed-meshheading:7541245-Ornithine Decarboxylase, pubmed-meshheading:7541245-Phosphotyrosine, pubmed-meshheading:7541245-Protein-Tyrosine Kinases, pubmed-meshheading:7541245-RNA, Messenger, pubmed-meshheading:7541245-Rats, pubmed-meshheading:7541245-Receptor, Epidermal Growth Factor, pubmed-meshheading:7541245-Transforming Growth Factor alpha, pubmed-meshheading:7541245-Tyrosine, pubmed-meshheading:7541245-Tyrphostins
pubmed:year
1995
pubmed:articleTitle
Identification and evaluation of the role of endogenous tyrosine kinases in azoxymethane induction of proliferative processes in the colonic mucosa of rats.
pubmed:affiliation
Department of Veterans Affairs, VA Medical Center, Allen Park, MI 48101, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.