Untersuchungen zur Expression von Zellzyklusregulatorproteinen in Zellinien und Geweben der Schilddrüse
Deregulation of cell cycle can potentially lead to uncontrolled cell growth and malignant transformation. P27, cyclin E and cyclin D3 control the G1/S-transition of cell cycle. Overexpression of cyclins or inactivation of an inhibitor of cyclin-dependent kinase-2 (p27) is linked with an autonomous proliferation of abberrant cells. The aim of the present study was to examine the expression of p27, cyclin E and cyclin D3 in 5 normal thyroid tissues (N), 15 undifferentiated thyroid carcinomas
... oid carcinomas (UTC), 21 papillary thyroid carcinomas (PTC), 16 follicular thyroid carcinomas (FTC), 2 follicular thyroid carcinoma cell lines (FTC 133, FTC 238) and 2 undifferentiated thyroid carcinoma cell lines (UTC C643, UTC 8505C). Western blot analysis revealed lower expression of p27 in N and UTC when compared to PTC and FTC. The highest expression levels of cyclin E were detected in FTC, whereas almost homogenous low expression was found in N, PTC and UTC. Cyclin D3 was highly expressed in majority of FTC and UTC. Normal thyroid tissues were cyclin D3 negative. No significant association between pTNM and expression of cell cycle proteins could be detected. Expression of cyclin E or cyclin D3 were further positively correlated with proliferation rate in thyroid carcinoma cell lines using MTT analysis, whereas p27 had no influence on tumor cell growth. In summary, these results suggest that cyclin E and cyclin D3 play an important role in regulation of proliferation in thyroid tumor cell lines. Loss of p27 may contributes to dedifferentiation in thyroid carcinomas. Additional studies are required to clarify the events in cell cycle involved in tumorigenesis and tumor behavior of thyroid cancer.