Expression status of Pin1 and cyclins in oral squamous cell carcinoma: Pin1 correlates with Cyclin D1 mRNA expression and clinical significance of cyclins

Phosphorylation on serine or threonine residue preceding proline (Ser/Thr-Pro) is a key regulatory mechanism. The conformation of certain phosphorylated Ser/Thr-Pro bonds is regulated specifically by the prolyl isomerase Pin1. It has been reported that Pin1 is strikingly overexpressed in a subset of human tumors. A differential-display screen reveals that Pin1 increases the transcription of several beta-catenin target genes, including those encoding cyclin D1 and c-Myc. Pin1 cooperates with Ras signaling in increasing the transcriptional activity of c-Jun towards cyclin D1. We have previously reported that Pin I is overexpressed in oral squamous cell carcinoma (OSCC) and its level correlates with Cyclin D1 expression. However, the analysis of the relationship between Pin1 and other cyclin genes has not been demonstrated in human OSCC. We examined Pin1 mRNA and protein expressions in OSCC cell lines, and analyzed Pin1/cyclins expression by RT-PCR. We report that Pin1 mRNA correlates with Cyclin D I mRNA expression and the expression of many cyclin genes is associated with lymph node metastasis in OSCC. These results indicate that Pin1 is a regulator of Cyclin D1 expression in OSCC and might have a role in oncogenesis; and the expression of many cyclin genes will be an indicator of lymph node metastasis in OSCC.