2 edition of p27(Kip1) is deregulated in tamoxifen resistant breast cancers through activation of receptor tyrosine kinases and cSrc kinases . found in the catalog.
p27(Kip1) is deregulated in tamoxifen resistant breast cancers through activation of receptor tyrosine kinases and cSrc kinases .
Isabel Milan Chu
Written in English
Here I show that the dual ErbB1/ErbB2 inhibitor, lapatinib (GW572016), can restore tamoxifen sensitivity in the ER positive cell lines: MCF-7 pr, T-47D and ZR-75. Restoration of tamoxifen response is associated with reduction of cyclin D1, increase of p27 and p27 associated with cyclin E-Cdk2 that is greater when the two drugs, lapatimb and tamoxifen, are used in combination, than with either alone. Lapatinib in combination with tamoxifen also effectively inhibited tamoxifen resistant MCF-7 xenografts.Similarly inhibition of cSrc with the cSrc/Abl specific inhibitor AZD0530 also restored tamoxifen sensitivity in a cSrc overexpressing, tamoxifen resistant cell line. I present evidence that cSrc phosphorylates p27 at tyrosine 74 and tyrosine 88 in vitro and in vivo. cSrc phosphorylated p27 shows reduced cyclin E-Cdk2 inhibition. cSrc transfection reduced cyclin E-Cdk2 bound p27. cSrc activated breast cancer lines show increased p27-cSrc complexes and cSrc siRNA and cSrc inhibitors increase cellular p27. cSrc activation upon mitogen stimulation coincides with increased cSrc-p27 co-precipitation in early G1 and precedes the loss of cyclin E-Cdk2 from p27. These data provide a strong rationale for further investigation of the therapeutic potential of cSrc and ErbB1/ErbB2 inhibitors combined with antiestrogens in the treatment of ER positive breast cancers.The estrogen receptor-blocking drug, tamoxifen is used for breast cancer to block the mitogenic effect of estrogen on breast cancer cells. Tamoxifen treatment activates the cyclin dependent kinase inhibitor, p27kip1 to mediate G1 arrest. However, initially responsive tumors invariably acquire resistance to treatment. This is often associated with increased expression of the epidermal growth factor receptor family members, ErbB1 and ErbB2. cSrc is activated by receptor tyrosine kinases and by cross talk with liganded estrogen receptor. Work of this thesis has shown that ErbB1, ErbB2 or cSrc overexpression can abrogate tamoxifen sensitivity in breast cancer lines through both reduction of p27 levels and inhibition of its function.
|The Physical Object|
|Number of Pages||131|
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It encodes a protein which belongs to the Cip/Kip family of cyclin dependent kinase (Cdk) inhibitor proteins. The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at consumersnewhomeconstruction.coms: CDKN1B, CDKN4, KIP1, MEN1B.
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Claus Richter, Head of Transaction Banking Solutions at Nordea, describes the collaborative approach of P27 and why the time is now right for developing a single payment area. Dec 20, · p27 is an inhibitor of cyclin dependent kinase involved in the regulation of the cell cycle.
In this commentary we discuss the current knowledge on p27 in breast cancer and its significance in predicting the outcome. p27 protein levels are high in most cases of breast carcinomas, are correlated with the levels of cyclin D1 and estrogen receptor, and could be a useful predictor of survival Cited by: However, p27 is dynamic, and can appear briefly in the cytoplasm during the G1-S transition prior to its degradation (Ref.
58). Curiously, in certain cell systems p21 and p27 have also been shown to have paradoxical roles in the regulation of the cell cycle. Oct 29, · The CDKN1B gene provides instructions for making a protein called p This protein is found in cells and tissues throughout the body.
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The CIP/KIP family is made up of three proteins: p21 cip1/waf1, P27 kip1, p57 kip2 These proteins share sequence homology at the N-terminal domain which allows them to bind to both the cyclin and CDK. Heartland RVs Prices, Values and Specs Select a Heartland RVs Series. Heartland RVs was founded in as a producer of high-end fifth wheel trailers.
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