d-609 and Pituitary-Neoplasms

d-609 has been researched along with Pituitary-Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for d-609 and Pituitary-Neoplasms

Article	Year
Fibroblast growth factors regulate prolactin transcription via an atypical Rac-dependent signaling pathway. Molecular endocrinology (Baltimore, Md.), 2003, Volume: 17, Issue:10 Fibroblast growth factors (FGFs) play a critical role in pituitary development and in pituitary tumor formation and progression. We have previously characterized FGF signal transduction and regulation of the tissue-specific rat prolactin (rPRL) promoter in GH4 pituitary cells. FGF induction of rPRL transcription is independent of Ras, but mediated by a protein kinase C-delta (PKCdelta)-dependent activation of MAPK (ERK). Here we demonstrate a functional role for the Rho family monomeric G protein, Rac1, in FGF regulation of PRL gene expression via an atypical signaling pathway. Expression of dominant negative Rac, but not RhoA or Cdc42, selectively inhibited FGF-induced rPRL promoter activity. Moreover, expression of dominant negative Rac also attenuated FGF-2 and FGF-4 stimulation of MAPK (ERK). However, in contrast to other Rac-dependent signaling pathways, FGF activation of rPRL promoter activity was independent of the c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase/Akt cascades. FGFs failed to activate JNK1 or JNK2, and expression of dominant negative JNK or Akt constructs did not block FGF-induced PRL transcription. Consistent with the role of PKCdelta in FGF regulation of PRL gene expression, activation of the rPRL promoter was blocked by an inhibitor of phospholipase Cgamma (PLCgamma) activity. FGF treatment also induced rapid tyrosine phosphorylation of PLCgamma in a Rac-dependent manner. These results suggest that FGF-2 and FGF-4 activate PRL gene expression via a novel Rac1, PLCgamma, PKCdelta, and ERK cascade, independent of phosphoinositol-3-kinase and JNK. Topics: Androstadienes; Animals; Bridged-Ring Compounds; Cell Line, Tumor; Chromones; Culture Media, Serum-Free; Fibroblast Growth Factor 2; Fibroblast Growth Factor 4; Fibroblast Growth Factors; Gene Expression Regulation; Isoenzymes; MAP Kinase Signaling System; Morpholines; Norbornanes; Phospholipid Ethers; Pituitary Neoplasms; Prolactin; Promoter Regions, Genetic; Protein Isoforms; Protein Kinase C; Protein Kinase C-delta; Proto-Oncogene Proteins; rac1 GTP-Binding Protein; Rats; Signal Transduction; Thiocarbamates; Thiones; Transcription, Genetic; Wortmannin	2003

Article

Year

Fibroblast growth factors regulate prolactin transcription via an atypical Rac-dependent signaling pathway.

Molecular endocrinology (Baltimore, Md.), 2003, Volume: 17, Issue:10

Fibroblast growth factors (FGFs) play a critical role in pituitary development and in pituitary tumor formation and progression. We have previously characterized FGF signal transduction and regulation of the tissue-specific rat prolactin (rPRL) promoter in GH4 pituitary cells. FGF induction of rPRL transcription is independent of Ras, but mediated by a protein kinase C-delta (PKCdelta)-dependent activation of MAPK (ERK). Here we demonstrate a functional role for the Rho family monomeric G protein, Rac1, in FGF regulation of PRL gene expression via an atypical signaling pathway. Expression of dominant negative Rac, but not RhoA or Cdc42, selectively inhibited FGF-induced rPRL promoter activity. Moreover, expression of dominant negative Rac also attenuated FGF-2 and FGF-4 stimulation of MAPK (ERK). However, in contrast to other Rac-dependent signaling pathways, FGF activation of rPRL promoter activity was independent of the c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase/Akt cascades. FGFs failed to activate JNK1 or JNK2, and expression of dominant negative JNK or Akt constructs did not block FGF-induced PRL transcription. Consistent with the role of PKCdelta in FGF regulation of PRL gene expression, activation of the rPRL promoter was blocked by an inhibitor of phospholipase Cgamma (PLCgamma) activity. FGF treatment also induced rapid tyrosine phosphorylation of PLCgamma in a Rac-dependent manner. These results suggest that FGF-2 and FGF-4 activate PRL gene expression via a novel Rac1, PLCgamma, PKCdelta, and ERK cascade, independent of phosphoinositol-3-kinase and JNK.

Topics: Androstadienes; Animals; Bridged-Ring Compounds; Cell Line, Tumor; Chromones; Culture Media, Serum-Free; Fibroblast Growth Factor 2; Fibroblast Growth Factor 4; Fibroblast Growth Factors; Gene Expression Regulation; Isoenzymes; MAP Kinase Signaling System; Morpholines; Norbornanes; Phospholipid Ethers; Pituitary Neoplasms; Prolactin; Promoter Regions, Genetic; Protein Isoforms; Protein Kinase C; Protein Kinase C-delta; Proto-Oncogene Proteins; rac1 GTP-Binding Protein; Rats; Signal Transduction; Thiocarbamates; Thiones; Transcription, Genetic; Wortmannin

2003