CYCLIN D1 AND CYCLIN-E EXPRESSION IN MALIGNANT THYROID-CELLS AND IN HUMAN THYROID CARCINOMAS

Evidence of the involvement of cyclin gene alterations in human cancer is growing. In this study, we! sought to determine the pattern of exp ression of cyclin D1 and cyclin E in normal and malignant thyroid cell s. Quiescent rat thyroid cells in culture, induced to synthesize DNA b y thyrotropin (TSH), expressed cyclin D1 gene after 6 hr and cyclin E gene with a peak at 18 hr from the stimulus; K-ras-transformed rat thy roid cells, which grew without addition of hormones necessary for norm al cell proliferation, expressed elevated levels of cyclin D1 and cycl in E, compared with normal differentiated thyroid cells. Human benign and malignant thyroid tumors and their relative normal tissues were th en analyzed. Neither major genetic alterations nor amplifications for cyclin D1 and cyclin E genes were found by Southern blot analysis in g enomic DNAs extracted from all types of thyroid tumors. Moreover, stat istical analyses of densitometric values from Northern blots did not s how increased levels of cyclin D1 and E mRNAs in the tumor samples, co mpared with normal thyroid. Immunohistochemical analyses of formalin-f ixed, paraffin-embedded sections of tissues with specific antibodies r evealed a prevalent cytoplasmic: cyclin E staining in the thyroid tiss ues analyzed. Cyclin D1, instead, was present in the cytoplasm of norm al thyroids and adenomas, but in 31% of thyroid papillary carcinomas a nalysed, it was overexpressed, with a localization in the nucleus. Our in vivo observations suggest that unlike cyclin E, elevated nuclear c yclin D1 expression defines a subset of thyroid papillary carcinomas, and might be a contributory factor to thyroid tumorigenesis. (C) 1998 Wiley-Liss, Inc.