Differential expression of cell cycle regulatory molecules and evidence for a “cyclin switch” during progression of prostate cancer

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Abstract
BACKGROUND Deregulation of the cell cycle can be viewed as both cause and consequence of cancer. Cyclin expression regulates progression through the cell cycle and although some cyclins have been examined in prostate cancer, the spatial and temporal changes in expression of these molecules during progression of autochthonous disease has not been fully explored. METHODS Expression patterns of cyclins and cyclin dependent kinases during the different stages of progression in the spontaneous autochthonous TRAMP model were examined by RNAse protection assay, Western blot analysis, and immunohistochemistry. RESULTS Differential expression of cell cycle regulatory molecules was observed during prostate cancer progression. Levels of the D-type cyclins decreased during progression while expression of cyclin E increased both at the mRNA and protein levels. The level of cyclin A and cyclin B expression increased beginning in early stage tumors and continued to increase throughout progression. The levels of cyclin dependent kinases did not change substantially during progression of the TRAMP model. CONCLUSIONS The spatial and temporal pattern of mitotic cyclin expression during prostate cancer progression suggests that these molecules represent potential therapeutic targets. The differential expression of D-type cyclins may have implications with respect to androgen receptor mediated gene expression.