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)

To define the molecular changes occurring in endocrine tumours, we have analysed three human endocrine tumours established in our laboratory: BON, a functioning carcinoid tumour from the pancreas; SIM, a nonfunctioning carcinoid of the ileum; and STAN, a pheochromocytoma. A homozygous point mutation of the N-ras gene was identified at codon 61 in BON cells in conjunction with overexpression of N-ras mRNA and protein. BON cells also exhibited increased expression of c-myc and cdc2 kinase mRNA and protein; TGF-beta 1, p53 and retinoblastoma (RB) mRNA and protein levels were decreased. In addition, increased expression of the mdm2 oncogene and both the truncated and the wild-type RB protein were noted in BON. SIM cells exhibited moderately increased N-ras and c-myc mRNA levels along with decreased levels of RB mRNA and protein. Similar to BON and SIM, analysis of STAN showed increased N-ras and c-myc levels. Our data show multiple molecular changes in the three human endocrine tumours with the BON cell line exhibiting the most dramatic changes. Furthermore, our data suggest the existence of different molecular pathways in the pathogenesis of endocrine tumours. These cell lines will provide unique in vitro models to further analyse the significance of these molecular alterations.
 ...
PMID:Analysis of multiple molecular changes in human endocrine tumours. 795 99

Constitutive expression of cyclin D1 is a frequent abnormality in human cancer and sustains the transformed phenotype. We have previously demonstrated that cyclin D1 is constitutively expressed in human BON neuroendocrine tumour cells due to an autocrine insulin-like growth factor-I (IGF-I) loop. Here we examine the regulation of cyclin D1 expression by endogenously released IGF-I in BON cells. Cyclin D1 expression in these cells was found to be dependent on phosphatidylinositol 3-kinase (PI3-K), but independent of the extracellular signal-regulated kinase cascade. Ras- and Rac-GTPases were found to be upstream activators of cyclin D1 expression, whereas protein kinase B/AKT and nuclear factor kappa B (NFkappaB) could be established as downstream mediators of cyclin D1 transcription in response to endogenously released IGF-I in these cells. In addition, the Ras/PI3-K/AKT/Rac/NFkappaB/cyclin D1 signaling cascade triggered by endogenously released IGF-I is sufficient to sustain Rb phosphorylation and cdk4 kinase activity in BON cells. In conclusion, our data provide the first comprehensive map of the signaling events elicited by endogenously released IGF-I leading to constitutive cyclin D1 expression in human neuroendocrine tumour cells.
 ...
PMID:Regulation of cyclin D1 expression by autocrine IGF-I in human BON neuroendocrine tumour cells. 1558 Feb 91