Abstract:
:The role of cyclic adenosine monophosphate (cAMP) is poorly understood in the regulation of normal and abnormal hepatic cell growth. In this study, we examined the regulation of intracellular cAMP levels and its effect on nuclear cAMP responsive elements (CREs) in a rat model of hepatocellular carcinoma (HCC). Tumorigenic liver cells were cultured from an in vivo model of HCC and the role of cAMP in cell mitogenesis determined. These data demonstrated agents that elevate intracellular cAMP ([cAMP]i) levels caused significant dose-dependent inhibition of serum-stimulated mitogenesis in HCC cells. Cells were next analyzed for transcription factor expression and activity following increased [cAMP]i. These data demonstrated time- and dose-dependent increases in CRE binding protein (pCREB) activity, a maximal response occurring after 10-20 min before returning to basal levels within 60 min. In contrast, increased [cAMP]i levels led to sustained inducible cAMP early repressor (ICER) II/IIgamma mRNA and protein induction. To understand these data in relation to the in vivo setting, HCC tumors were analyzed and compared to pair-matched normal liver (NL) samples. These studies demonstrated significantly elevated Gsalpha-protein expression in HCC versus NL in the absence of significant changes in basal cAMP levels. Analysis of total and active CREB demonstrated significantly increased total CREB/pCREB in HCC versus NL. Further analysis of CRE expression demonstrated significantly increased expression of ICER mRNA and protein in HCC versus sham operated (Sh). These data demonstrate cAMP, while capable of stimulating promitogenic CREB activation inhibits cell mitogenesis in HCC possibly via ICER induction.
journal_name
J Cell Physioljournal_title
Journal of cellular physiologyauthors
Kovach SJ,Price JA,Shaw CM,Theodorakis NG,McKillop IHdoi
10.1002/jcp.20474keywords:
subject
Has Abstractpub_date
2006-02-01 00:00:00pages
411-9issue
2eissn
0021-9541issn
1097-4652journal_volume
206pub_type
杂志文章abstract::Programmed cell death in mammary tissue was studied during natural weaning in lactating mice and after litter removal or milk stasis. All treatments stimulated mammary apoptosis, indicating that this process is an integral part of the tissue's involution after lactation. Induction of apoptosis was slower in natural we...
journal_title:Journal of cellular physiology
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abstract::The polyphenolic compounds curcumin and quercetin increased sensitivity of ovarian cancer cells (CAOV3 and SKOV3) to cisplatin. The effect was obtained when the compounds were added simultaneously with cisplatin, as well as when they were added 24 h before. High serum levels of certain cytokines, for example interleuk...
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更新日期:1981-05-01 00:00:00
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更新日期:2015-11-01 00:00:00
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更新日期:1982-03-01 00:00:00
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更新日期:1991-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2019-08-01 00:00:00
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journal_title:Journal of cellular physiology
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更新日期:1984-01-01 00:00:00
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更新日期:2017-12-01 00:00:00
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更新日期:2017-05-01 00:00:00
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journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1040890103
更新日期:1976-09-01 00:00:00
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abstract::The transport of L-alanine in human diploid fibroblasts was investigated. Transport measurements were performed on subcultures between the third and eighth passages with subconfluent cells growing on glass coverslips. Kinetic analysis of approximate initial rates of transport at substrate concentrations from 0.05 to 1...
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更新日期:1991-01-01 00:00:00
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