Purpose: Cell cycle regulation, which is important for normal cellular proliferation, is controlled by a complex network of intracellular proteins, with cyclins, cyclin-dependent kinases (CDKs) and cyclin-dependent kinase inhibitors (CD-KIs) playing a central role. This equilibrium is interrupted in cancer cells, resulting in uncontrolled cellular proliferation.
Methods: In the present study we examined, by means of semi-quantitative RT-PCR, the expression of G(1)-phase cell cycle regulators MDM2, E2F1, Cyclin D1 (CCND1), CDK4, p19(INK4D), p21(WAF1/CIP1) and p27(KIP1) in a series of 32 bladder cancer specimens paired with adjacent normal tissues.
Results: Cyclin D1 was overexpressed in 10/32 (31.2%) and downregulated in 8/32 (25.0%) bladder cancer specimens. Additionally, p21 was overexpressed in 9/32 (28.1%) and downregulated in 10/32 (31.3%) cancer samples. On the contrary, MDM2, E2F1, CDK4, p19 and p27 expression was normal in the majority of malignant specimens. Further statistical analysis revealed significant associations between increased p21 levels and bladder cancer patients with no exposure to chemicals (p=0.048), as well as with patients with no artificial sweetener intake (p=0.012), and between increased Cyclin D1 levels and study subjects with no artificial sweetener intake (p=0.012).
Conclusion: Based on these results, we conclude that Cyclin D1 and p21 mRNA deregulation seems to be an important event in bladder carcinogenesis. However, further studies are needed, in order to determine whether these two cell cycle regulators can be used as markers for the early detection of bladder cancer and to monitor its progression and recurrence.