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.