Linked Life Data

9591782

Source:http://linkedlifedata.com/resource/pubmed/id/9591782

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
1998-5-28
pubmed:abstractText
We have examined the influence of insulin-like growth factor I (IGF-1) on prolactin gene expression in rat pituitary GH4C1 cells. Incubation with IGF-1 increases prolactin mRNA levels and activates the prolactin promoter in transient transfection assays. A similar degree of activation is observed with constructs extending to -3000 and -176 base pairs of the prolactin 5' flanking region, indicating that the IGF-1 response element is located in the proximal promoter sequences. A plasmid containing 101 base pairs shows a partial stimulation by IGF-1, and the response is lost in a deletion to -76 base pairs. The Ras oncoproteins have been implicated as a critical signaling component in mediating the effect of growth factor receptor tyrosine kinases. Expression of oncogenic RasVal12 mimics the effect of IGF-1 on the prolactin promoter, and a dominant negative Ras, RasAsn17, blocks IGF-1-mediated stimulation. Dominant negative mitogen-activated protein kinase (MAPK) also reduces the activation of the prolactin promoter by IGF-1. Ets transcription factors have been described to lie downstream of Ras and MAPK in the signaling pathway leading to prolactin gene activation. Mutation of two Ets binding sites in the promoter region between -101 and -76 abolishes the response to IGF-1. Furthermore, a dominant negative Ets vector strongly reduces the response of the prolactin promoter to IGF-1 and Ras. The endogenous concentration of Ets-related proteins is not limiting in GH4C1 cells for the IGF-1 effect. However, c-Ets-1 and GHF-1 act synergistically in HeLa cells with the IGF-1 receptor, reconstituting pituitary IGF-1 responsiveness. The response to IGF-1 in GH4C1 cells is still observed after transfection with RasVal12 suggesting that, although Ras is required, IGF-1 could stimulate other pathway/s in addition to Ras. Wortmanin, an inhibitor of phosphatidylinositol-3 kinase (PI-3 kinase), also prevents the response of the prolactin promoter to IGF-1. These results show that both the Ras/MAPK/Ets pathway, as well as the activation of PI-3 kinase are involved in the signaling mechanism leading to prolactin expression by IGF-1 in GH4C1 cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1981-91
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Insulin-like growth factor-1 stimulates rat prolactin gene expression by a Ras, ETS and phosphatidylinositol 3-kinase dependent mechanism.
pubmed:affiliation
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't