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Old 10-29-2009, 06:24 AM   #1
Hopeful
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Join Date: Aug 2006
Posts: 3,380
Discovery of a selective Cyclin D Kinase Inhibitor that inhibts +++ bc in vitro

http://breast-cancer-research.com/co...df/bcr2419.pdf

"Cell lines representing luminal estrogen receptor-positive (ER+) subtype (including those that are HER2 amplified) were most sensitive to growth inhibition by PD 0332991 while non-luminal/basal subtypes were most resistant. ANOVA identified 450 differentially expressed genes between sensitive and resistant cells. pRb and Cyclin D1 were elevated and CDKN2A (p16) was decreased in the most sensitive lines. Cell cycle analysis showed G0/G1 arrest in sensitive cell lines and Western blot analysis demonstrated that Rb phosphorylation is blocked in sensitive lines but not resistant lines. PD 0332991 was synergistic with tamoxifen and trastuzumab in ER+ and HER2 amplified cell lines, respectively. PD 0332991 enhanced sensitivity to tamoxifen in cell lines with conditioned resistance to ER blockade."

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