Matches in SemOpenAlex for { <https://semopenalex.org/work/W2149111421> ?p ?o ?g. }
- W2149111421 endingPage "378" @default.
- W2149111421 startingPage "371" @default.
- W2149111421 abstract "Guanine nucleotide regulatory proteins (G-proteins) represent an important transmembrane pathway whereby extra-cellular signals are transduced to intracellular signaling pathways. The mitogen-activated protein kinase (MAPK) cascade has been identified as a key factor in transducing numerous mitogenic stimuli. MAPK activity is regulated via numerous receptor types, including those linked to Gq/G11-proteins, which regulate phospholipase-C activity. We hypothesized that alterations in a Gq/G11-PLC pathway may contribute to the enhanced cellular mitogenesis characteristic of hepatocellular carcinoma (HCC), possibly via a MAPK-dependent pathway. By using an in vivomodel of HCC we investigated changes in Gq/G11-protein expression in tumorigenic tissue versus adjacent, non-neoplastic liver. In addition we addressed the role of Gq/G11-proteins in the regulation of MAPK-linked mitogenesis by using rat hepatic tumorigenic cells (H4IIE) and isolated hepatocytes in culture. Western blot analysis showed significant increases in Gqα and G11α expression in tumorigenic liver versus normal liver specimens, an effect that was augmented in cultured H4IIE cells versus isolated cultured hepatocytes. Furthermore, phosphoinositol specific phospholipase-C (PLC) activity was significantly increased in HCC versus normal liver. A specific PLC inhibitor (Et-18-OCH3) caused a dose-dependent decrease in serum stimulated DNA synthesis in both cultured H4IIE cells and isolated rat hepatocytes, the H4IIE cell line showing greater sensitivity to Et-18-OCH3. In addition, serum-stimulated MAPK activity was significantly enhanced in H4IIE versus cultured hepatocytes. Moreover, treatment with Et-18-OCH3significantly attenuated serum stimulated MAPK activity in both cultured hepatocytes and H4IIE cells. Furthermore, U73122 (Gqα-PLC specific uncoupler) and GP2A (Gqα specific inhibitor) mirrored the effects of those observed for Et-18-OCH3 whereas PD98059 (specific MEK inhibitor) completely abolished serum-stimulated DNA synthesis in tumorigenic H4IIE cells. We conclude that HCC is associated with enhanced Gq/G11-PLC expression/activity as compared with normal liver. Furthermore, a PLC-linked MAPK cascade plays a significant role in the progression of the enhanced mitogenesis characteristic of HCC." @default.
- W2149111421 created "2016-06-24" @default.
- W2149111421 creator A5015843387 @default.
- W2149111421 creator A5019656476 @default.
- W2149111421 creator A5070315270 @default.
- W2149111421 creator A5075291075 @default.
- W2149111421 date "1999-02-01" @default.
- W2149111421 modified "2023-09-26" @default.
- W2149111421 title "Altered Gq/G11 guanine nucleotide regulatory protein expression in a rat model of hepatocellular carcinoma: Role in mitogenesis" @default.
- W2149111421 cites W1490154674 @default.
- W2149111421 cites W1506520436 @default.
- W2149111421 cites W1522965874 @default.
- W2149111421 cites W1573821584 @default.
- W2149111421 cites W1577631465 @default.
- W2149111421 cites W1600553288 @default.
- W2149111421 cites W1967385667 @default.
- W2149111421 cites W1974366727 @default.
- W2149111421 cites W1975915718 @default.
- W2149111421 cites W1981388207 @default.
- W2149111421 cites W1990401009 @default.
- W2149111421 cites W2021148197 @default.
- W2149111421 cites W2025983714 @default.
- W2149111421 cites W2034589498 @default.
- W2149111421 cites W2044835236 @default.
- W2149111421 cites W2051357160 @default.
- W2149111421 cites W2051750791 @default.
- W2149111421 cites W2052016477 @default.
- W2149111421 cites W2057437595 @default.
- W2149111421 cites W2059817797 @default.
- W2149111421 cites W2068502127 @default.
- W2149111421 cites W2075409812 @default.
- W2149111421 cites W2088823687 @default.
- W2149111421 cites W2090551110 @default.
- W2149111421 cites W2090575139 @default.
- W2149111421 cites W2091753578 @default.
- W2149111421 cites W2092014913 @default.
- W2149111421 cites W2093621392 @default.
- W2149111421 cites W2098046058 @default.
- W2149111421 cites W2151477904 @default.
- W2149111421 cites W2164123016 @default.
- W2149111421 cites W4292820908 @default.
- W2149111421 cites W4293247451 @default.
- W2149111421 doi "https://doi.org/10.1002/hep.510290201" @default.
- W2149111421 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9918912" @default.
- W2149111421 hasPublicationYear "1999" @default.
- W2149111421 type Work @default.
- W2149111421 sameAs 2149111421 @default.
- W2149111421 citedByCount "9" @default.
- W2149111421 countsByYear W21491114212015 @default.
- W2149111421 countsByYear W21491114212017 @default.
- W2149111421 countsByYear W21491114212020 @default.
- W2149111421 crossrefType "journal-article" @default.
- W2149111421 hasAuthorship W2149111421A5015843387 @default.
- W2149111421 hasAuthorship W2149111421A5019656476 @default.
- W2149111421 hasAuthorship W2149111421A5070315270 @default.
- W2149111421 hasAuthorship W2149111421A5075291075 @default.
- W2149111421 hasBestOaLocation W21491114211 @default.
- W2149111421 hasConcept C153911025 @default.
- W2149111421 hasConcept C184235292 @default.
- W2149111421 hasConcept C202751555 @default.
- W2149111421 hasConcept C2776200302 @default.
- W2149111421 hasConcept C2778597717 @default.
- W2149111421 hasConcept C502942594 @default.
- W2149111421 hasConcept C54355233 @default.
- W2149111421 hasConcept C552990157 @default.
- W2149111421 hasConcept C55493867 @default.
- W2149111421 hasConcept C57074206 @default.
- W2149111421 hasConcept C62478195 @default.
- W2149111421 hasConcept C64241487 @default.
- W2149111421 hasConcept C81885089 @default.
- W2149111421 hasConcept C86803240 @default.
- W2149111421 hasConcept C95444343 @default.
- W2149111421 hasConcept C97029542 @default.
- W2149111421 hasConceptScore W2149111421C153911025 @default.
- W2149111421 hasConceptScore W2149111421C184235292 @default.
- W2149111421 hasConceptScore W2149111421C202751555 @default.
- W2149111421 hasConceptScore W2149111421C2776200302 @default.
- W2149111421 hasConceptScore W2149111421C2778597717 @default.
- W2149111421 hasConceptScore W2149111421C502942594 @default.
- W2149111421 hasConceptScore W2149111421C54355233 @default.
- W2149111421 hasConceptScore W2149111421C552990157 @default.
- W2149111421 hasConceptScore W2149111421C55493867 @default.
- W2149111421 hasConceptScore W2149111421C57074206 @default.
- W2149111421 hasConceptScore W2149111421C62478195 @default.
- W2149111421 hasConceptScore W2149111421C64241487 @default.
- W2149111421 hasConceptScore W2149111421C81885089 @default.
- W2149111421 hasConceptScore W2149111421C86803240 @default.
- W2149111421 hasConceptScore W2149111421C95444343 @default.
- W2149111421 hasConceptScore W2149111421C97029542 @default.
- W2149111421 hasIssue "2" @default.
- W2149111421 hasLocation W21491114211 @default.
- W2149111421 hasLocation W21491114212 @default.
- W2149111421 hasOpenAccess W2149111421 @default.
- W2149111421 hasPrimaryLocation W21491114211 @default.
- W2149111421 hasRelatedWork W1976734851 @default.
- W2149111421 hasRelatedWork W1990580490 @default.
- W2149111421 hasRelatedWork W2004726042 @default.
- W2149111421 hasRelatedWork W2095169768 @default.