Cell cyclins: triggering elements of cancer or not?

Abstract

Cyclins are indispensable elements of the cell cycle and derangement of their function can lead to cancer formation. Recent studies have also revealed more mechanisms through which cyclins can express their oncogenic potential. This review focuses on the aberrant expression of G1/S cyclins and especially cyclin D and cyclin E; the pathways through which they lead to tumour formation and their involvement in different types of cancer. These elements indicate the mechanisms that could act as targets for cancer therapy.

Gastroesophageal Reflux Disease: Molecular Predictors in Neoplastic Progression of Barrett's Esophagus

“…Cyclins bind to CDKs and lead to phosphorylation of proteins necessary for progression through the cell cycle (Stamatakos et al, 2010). In addition to these regulators, p21 acts as a cyclin dependent kinase inhibitor in tumor suppression as well as a possible oncogene, inhibiting apoptosis and promoting proliferation (Abbas and Dutta, 2009;Gartel, 2006).…”

“…P21 has been described initially in the tumor suppression cascade of p53 as described above, however new research suggests that it may also have the opposite action as an oncogene promoting tumorinogensis (Gartel, 2006). Cyclin D1 has been implicated in a number of cancers and is overexpressed due to derangements that include chromosomal translocations, gene amplification and anomalies in proper intercellular trafficking and proteolysis (Kim and Diehl, 2009;Stamatakos et al, 2010). When overexpressed cyclin D1 leads to tumor formation through several mechanisms.…”

“…Third cyclin D1 also has non-CDK dependent actions including increasing estrogen receptor transcription (Neuman et al, 1997) as well as abnormalities in the repression of PPARγ, a transcriptional protein modulated by abnormal binding of HDAC by cyclin D1 (Fu et al, 2005). In addition cyclin D1 has been reported to lead to increased expression of fibroblast growth factor 1 (Tashiro et al, 2007) as well as increased production of reactive oxygen species (ROS) leading to metastasis of tumors (Stamatakos et al, 2010). Although the exact mechanism of action in EAC has not been completely elucidated, studies have demonstrated cyclin D1 overexpression in BE and early stages of tumorigensis (Arber et al, 1996;Bani-Hani et al, 2000).…”

Expression of cyclin E in stage III colorectal carcinoma

“…Conversely, impaired activity of the cyclin E/CDK2 complex arrests the cell before new DNA is synthesized. The precisely timed degradation of cyclins is one of the mechanisms that regulate CDK activity, which is necessary for coordination of the cell cycle and may prevent the development of cancer cells (7,8). Cyclin E overexpression increases cell proliferation via enforced progression to S phase and may lead to carcinogenesis (9).…”

“…The cyclin E gene is overexpressed, and protein concentrations and related kinase activity are often altered, in numerous human tumors. Impaired expression of cyclin E has been identified in breast, ovarian, gastric, colorectal and non-small lung cancers, leukemias, lymphomas and melanomas (7,(10)(11)(12)(13)(14)(15)(16)(17).…”