E- and A-type cyclins as markers for cancer diagnosis and prognosis

Abstract

Cyclin-dependent kinase (CDK)2 interacting cyclins perform essential functions for DNA replication and cellular proliferation. The human genome encodes two E-type cyclins (E and E2) and two A-type cyclins (A1 and A2). Dysregulation of the CDK2-bound cyclins plays an important role in the pathogenesis of cancer. Cyclin A2 is associated with cellular proliferation and can be used for molecular diagnostics as a proliferation marker. In addition, cyclin A2 expression is associated with a poor prognosis in several types of cancer. Cyclin A1 is a tissue-specific cyclin that is highly expressed in acute myeloid leukemia and in testicular cancer. High levels of cyclin E expression are found in many types of cancer. Overexpression of cyclin E at the mRNA level can be based on gene amplification and transcriptional mechanisms. In addition, proteolytically cleaved forms of cyclin E that show oncogenic functions have been described. Cyclin E plays a critical role for G1/S transition. Its overexpression is not only associated with proliferation but rather indicates a more malignant phenotype which is likely to be linked to the induction of chromosomal instability. These biological functions of cyclin E relate to a poor prognosis when high cyclin E levels are found. The link between cyclin E and poor prognosis is well established in breast and lung cancer but is likely to be observed in other cancers as well. The second E-type cyclin, cyclin E2, has been shown to be overexpressed in breast cancers although the potential role as a diagnostic or prognostic marker is unknown. This review provides an overview of the potential of cyclins E and A as markers for diagnosis and prognosis in human cancer.