Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of oncogenesis is extremely complicated and controlled by various factors, most of which are based on cell proliferation, tumor invasion, neovascularization, and inhibition of apoptosis. We have investigated the relationship between thirty three oncogenes expression and histopathological prognostic factors of endometrial carcinomas, including clinical stage, histological grade, presence of invasion to greater than one-half the myometrium, clinical outcome, and survival rate. Scoring on the basis of the percentage of positive cells indicated that Plks, EphB4, ephrin-B2, Id1, CaMKIV, c-Ets1, Elf-1, and survivin expression were significantly associated with PCNA-labeling index, clinical stage, histological grade, the presence of invasion to greater than one-half the myometrium, and clinical outcome. Survival data were available for all patients, and univariate Cox regression analysis showed that Plks, CaMKIV, Elf-1, and survivin expression were significantly associated with poor prognosis. Our results demonstrate that some oncogenes expression in endometrial carcinoma correlate with the malignant potential of these tumors. Thus, in addition to being of diagnostic value, modulation of these oncogenes activity in the tumors by chemotherapeutic agents or gene therapy may prove to be of therapeutic value. In this review, we demonstrate the biologic behavior of seven novel molecules (Plks, Eph/ephrin, Id family, CaMK, c-Ets1, Elf-1, and survivin) in the endometrial carcinoma.
 ...
PMID:The relationship between oncogene expression and clinical outcome in endometrial carcinoma. 1537 36

B-cell activating factor (BAFF) is a crucial survival factor for B cells, and excess BAFF contributes to development of autoimmune diseases. Recent studies have shown that rapamycin can prevent BAFF-induced B-cell proliferation and survival, but the underlying mechanism remains to be elucidated. Here we found that rapamycin inhibited human soluble BAFF (hsBAFF)-stimulated cell proliferation by inducing G1-cell cycle arrest, which was through downregulating the protein levels of CDK2, CDK4, CDK6, cyclin A, cyclin D1, and cyclin E. Rapamycin reduced hsBAFF-stimulated cell survival by downregulating the levels of anti-apoptotic proteins (Mcl-1, Bcl-2, Bcl-xL and survivin) and meanwhile upregulating the levels of pro-apoptotic proteins (BAK and BAX). The cytostatic and cytotoxic effects of rapamycin linked to its attenuation of hsBAFF-elevated intracellular free Ca2+ ([Ca2+]i). In addition, rapamycin blocked hsBAFF-stimulated B-cell proliferation and survival by preventing hsBAFF from inactivating PTEN and activating the Akt-Erk1/2 pathway. Overexpression of wild type PTEN or ectopic expression of dominant negative Akt potentiated rapamycin's suppression of hsBAFF-induced Erk1/2 activation and proliferation/viability in Raji cells. Interestingly, PP242 (mTORC1/2 inhibitor) or Akt inhibitor X, like rapamycin (mTORC1 inhibitor), reduced the basal or hsBAFF-induced [Ca2+]i elevations. Chelating [Ca2+]i with BAPTA/AM, preventing [Ca2+]i elevation using EGTA, 2-APB or verapamil, inhibiting CaMKII with KN93, or silencing CaMKII strengthened rapamycin's inhibitory effects. The results indicate that rapamycin inhibits BAFF-stimulated B-cell proliferation and survival by blunting mTORC1/2-mediated [Ca2+]i elevations and suppressing Ca2+-CaMKII-dependent PTEN/Akt-Erk1/2 signaling pathway. Our finding underscores that rapamycin may be exploited for prevention of excessive BAFF-induced aggressive B-cell malignancies and autoimmune diseases.
 ...
PMID:Rapamycin inhibits B-cell activating factor (BAFF)-stimulated cell proliferation and survival by suppressing Ca2+-CaMKII-dependent PTEN/Akt-Erk1/2 signaling pathway in normal and neoplastic B-lymphoid cells. 3206 91