title: Cell cycle regulation and its aberrations in human lung carcinoma.
abstract: Cell cycle is strictly regulated by complex and redundant mechanisms. Basically, cell cycle transition is promoted by accelerator molecules termed 'cyclin' and 'cyclin-dependent kinase' (cdk), and inhibited by brake molecules termed 'cdk-inhibitor' (CKI). Although based on the results of early experimental studies and of clinicopathological analyses, there was much speculation that gene aberration of those molecules would be common; this has not turned out to be the case. One reason may be that activation or inactivation of a single molecule by itself usually does not lead to cell transformation, but rather to apoptosis. Successful transformation and unchecked cell proliferation appears to require the coordinated up-regulation of cyclin/cdk and/or suppression of CKI. In this article, I focus on the precise regulation of the cell cycle and describe abnormalities found in these proteins in lung carcinoma. Notable findings in lung carcinoma include: (i) cyclin A/cdk2 plays a key role in cell proliferation, while protein amount of cyclin E does not necessarily reflect cellular proliferative activity, depending on the tumor type; (ii) CKI function not only as suppressors, but also as activators of cdk, depending on expression levels; and (iii) aberrant expression of cyclin/cdk can lead to apoptosis in vivo in humans. Another key point is that as lung carcinoma is composed of a mixture of heterogeneous histological subtypes, the growth control of carcinoma cells is diversely regulated, depending on each histological subtype. This diversity is also described with our experimental results.
authors.affiliation: Department of Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan. ydobashi@yamanashi.med.ac.jp
authors.forename: Yoh
authors.initials: Y
authors.lastname: Dobashi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D018844:Cyclin-Dependent Kinases