HUMAN CYCLIN D1 ONCOGENE AND ESOPHAGEAL SQUAMOUS-CELL CARCINOMA

Background. Oncogene activation and tumor suppressor gene inactivation have been implicated in the genetic basis of esophageal squamous cell carcinoma (ESCC). Cyclin D1, an oncogene that has a critical role in G1 progression of the cell cycle, has been observed to be amplified in carcinomas of the breast and head and neck, and translocated in parat hyroid adenomas and centrocytic lymphomas. Methods. Established ESCC c ell lines were assayed for cyclin D1 amplification and overexpression by Southern, Northern, and Western blot analyses. In addition, cyclin D1 overexpression was determined in primary tumors and adjacent normal mucosa by differential polymerase chain reaction (PCR) and immunohist ochemical staining. Results. The authors observed that approximately 5 0% of ESCC cell lines with cyclin D1 DNA amplification also had RNA an d protein overexpression. Related genes, cyclin D2 and D3, were not am plified or overexpressed in these cell lines with rare exception. The cyclin D1 protein was able to associate with the cell-cycle-dependent kinases, cdk4 and cdk6, but not always with proliferating cell nuclear antigen in selected cell lines tested, representing a novel finding. In addition, approximately 50% of primary tumors had cyclin D1 overexp ression that was not present in adjacent normal mucosa. Cyclin D1 over expression based on PCR correlated with enhanced cyclin D1 protein nuc lear staining in malignant cells. Conclusion. Cyclin D1 is amplified a nd overexpressed in ESCC and may be important in its molecular pathoge nesis.