Cell cycle regulation and its aberrations in human lung carcinoma.
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.
Dobashi
Yoh
Y
Department of Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan. ydobashi@yamanashi.med.ac.jp
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
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D018844:Cyclin-Dependent Kinases