Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to investigate the effect of bone morphogenetic protein (BMP-7) on thyroid carcinoma cell growth. Addition of BMP-7 inhibited the proliferation of four out of six human anaplastic thyroid carcinoma cell lines, observed as decreased incorporation of (3)H-thymidine and decreased cell number. The growth inhibitory effect was cell density-dependent; sparse cells were inhibited by BMP-7 whereas dense cells were not. Cell cycle analysis by flow cytometry showed an increased fraction of cells in the G1-phase and subsequent decrease in both S- and G2/M-phase after BMP-7 stimulation. Furthermore, BMP-7 caused an upregulation of the cyclin-dependent kinase inhibitors (CDKIs) p21 and p27, decreased activity of Cdk2 and Cdk6, and hypophosphorylation of the retinoblastoma protein (pRb). These findings suggest a growth inhibitory effect of BMP-7 on anaplastic thyroid carcinoma cells by inhibition of Cdk activity shifting the Rb protein to the hypophosphorylated state.
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PMID:BMP-7-induced cell cycle arrest of anaplastic thyroid carcinoma cells via p21(CIP1) and p27(KIP1). 1145 59

Fibroblast proliferation, differentiation, and migration contribute to the characteristic pulmonary vascular remodeling seen in primary pulmonary hypertension (PPH). The identification of mutations in the bone morphogenetic protein type II receptor (BMPRII) in PPH have led us to question what role BMPRII and its ligands play in pulmonary vascular remodeling. Thus, to further understand the functional significance of BMPRII in the pulmonary vasculature, we examined the expression of TGF-beta superfamily receptors in human fetal lung fibroblasts (HFL) and investigated the role of BMP4 on cell cycle regulation, fibroblast proliferation, and differentiation. Furthermore, signaling pathways involved in these processes were examined. HFL expressed BMPRI and BMPRII mRNA and demonstrated specific I(125)-BMP4 binding sites. BMP4 inhibited [(3)H]thymidine incorporation and proliferation of HFL; protein expression was increased for the cell cycle inhibitor p21 and reduced for the positive regulators cyclin D and cdk2 by BMP4. BMP4 induced differentiation of HFL into a smooth muscle cell phenotype since protein expression of alpha-smooth muscle actin and smooth muscle myosin was increased. Furthermore, p38(MAPK), ERK1/2, JNK, and Smad1 were phosphorylated by BMP4. Using specific MAPK inhibitors, a dominant negative Smad1 construct, and Smad1 siRNA, we found that the antiproliferative and prodifferentiation effects of BMP4 were Smad1 dependent with JNK also contributing to differentiation. Because failure of Smad phosphorylation is a major feature of BMPRII mutations, these results imply that BMPRII mutations may promote the expansion of fibroblasts resistant to the antiproliferative, prodifferentiation effects of BMPs and suggest a mechanism for the vascular obliteration seen in familial PPH.
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PMID:BMP4 inhibits proliferation and promotes myocyte differentiation of lung fibroblasts via Smad1 and JNK pathways. 1551 92

Prostate cancer is one of the most common cancers in men. Several lines of evidence have suggested that bone morphogenetic protein (BMP) signals play important roles in the generation and progression of prostate cancers. In the present study, we show that BMP-7 inhibits the proliferation of androgen-insensitive PC-3 and DU-145 prostate cancer cells in a medium containing 1% fetal bovine serum, observed as decreased incorporation of [(3)H]thymidine and decreased cell number. Cell cycle analysis by flow cytometry showed an increased fraction of cells in the G1 phase and subsequent decrease in both S and G2/M phase after BMP-7 stimulation. BMP-7 caused an upregulation of the cyclin-dependent kinase inhibitor (CDKI) p21(CIP1/WAF1), and decreased the activity of Cdk2, leading to hypophosphorylation of Rb proteins. Furthermore, in order to evaluate the impact of BMP signals on prostate tumor growth, we generated the PC-3 cell lines expressing a constitutively active BMP type I receptor (constitutively active (c.a.) activin receptor-like kinase (ALK)-6) in a tetracycline (Tet)-regulated manner. Tet/doxycycline-regulated expression of c.a.ALK-6 resulted in the inhibition of in vitro cell proliferation and reduction of the size of tumors derived from the PC-3 cells subcutaneously injected into immune-deficient mice. Collectively, these findings suggest that BMP signals inhibit growth and proliferation of prostate tumor cells through induction of CDKI. Furthermore, this is the first report of a role for BMP signaling in reducing growth kinetics of androgen-insensitive prostate tumors.
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PMID:BMP signals inhibit proliferation and in vivo tumor growth of androgen-insensitive prostate carcinoma cells. 1553 27