Abstract:
:Cyclic AMP (cAMP) analogues that selectively bind to either one of the two binding sites of cAMP-dependent protein kinase demonstrate a potent inhibition of the growth stimulated by estrogen in MCF-7 human breast-cancer cells in culture. The site-selective analogues, which are more potent activators of protein kinase than the analogues studied earlier, exhibit growth inhibition at micromolar concentrations. Among the analogues tested, 8-Cl-cAMP (Site I-selective) and N6-benzyl-cAMP (Site 2-selective) are the 2 most potent inhibitors, causing 40-70% inhibition of the estrogen-stimulated growth at 10-20 microM concentrations with no sign of toxicity. 8-Cl-cAMP (1 microM) in combination with N6-benzyl-cAMP (0.5 microM) almost completely blocks estrogen-stimulated growth, demonstrating synergism between the Site 1- and Site 2-selective analogues. The growth inhibition parallels an increase in the R11 cAMP receptor protein with a decrease in the R1 receptor as well as reduction of c-myc and c-ras oncoproteins, whereas growth inhibition by tamoxifen does not affect the levels of the cAMP receptor proteins or the c-myc and c-ras protein levels. Site-selective cAMP analogues are antagonistic to estrogen stimulation of breast-cancer cell growth through a mechanism different from that of tamoxifen.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Katsaros D,Ally S,Cho-Chung YSdoi
10.1002/ijc.2910410616subject
Has Abstractpub_date
1988-06-15 00:00:00pages
863-7issue
6eissn
0020-7136issn
1097-0215journal_volume
41pub_type
杂志文章abstract::Chromosome 17 is a frequent target during breast-cancer formation and progression. It has been shown to be affected by allele losses at multiple sites, as well as by DNA amplification. Our aim was to delineate a map of the genetic alterations on chromosome 17 in a given set of breast tumors. To this end we analyzed 15...
journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
pub_type: 杂志文章,多中心研究
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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