This finding suggested that inhibition of CDK2 and pRb expression via upregulated p21 was involved in the downregulation of Pim-2-induced G<sub>0</sub>/G<sub>1</sub> cell cycle arrest in lung cancer and hematopoietic malignancy cells.
These effects may result from the ability of miR-5100 to promote G1/S transition and downregulate cyclin D1 and cyclin-dependent kinases 2 (CDK2) expressions in lung cancer stable cells.
We previously reported that CDK2 antagonism causes lung cancer cells to undergo anaphase catastrophe and apoptosis through inhibition of phosphorylation of the centrosomal protein CP110.
We previously discovered that CDK2 inhibition causes lung cancer cells with more than two centrosomes to undergo multipolar cell division leading to apoptosis, defined as anaphase catastrophe.
The known cellular functions of the tumor suppressor genes most commonly affected in lung cancer are reviewed herein, including the retinoblastoma (Rb) gene on chromosome 13q14, the p53 gene on 17p13, and the cyclin-dependent kinase inhibitor (CDKN2) gene on 9p21.
Both copies of the candidate tumor suppressor gene on chromosome 9, CDKN2, are deleted in approximately one-fourth of lung cancer cell lines examined and the protein product of CDKN2, p16 is undetectable in one-third of the lung cancer cell lines studied.
In summary, inactivation of CDKN2 is implicated in the development of about 20% of NSCLC, but the possibility of another tumor suppressor gene on chromosome segment 9p21 important in lung cancercannot be eliminated.
One half of all cancer cell lines and one fourth of lung cancer cell lines examined to date contain homozygous deletions (i.e., both alleles lost) of CDKN2.