CELL CYCLE-RELATED VARIATION AND TISSUE-RESTRICTED EXPRESSION OF HUMAN CYCLIN D1 PROTEIN

Recent evidence from genetic studies suggests that abnormalities of so me of the members of the cyclin superfamily may be intimately associat ed with tumourigenesis, most likely through deregulation of the cell c ycle control. In an attempt to elucidate the potential role of cyclin D1 (a gene located within the 11q13 amplicon and a candidate BCL-1, PR AD-1 oncogene) in the pathogenesis of human neoplasias, we have develo ped and characterized a novel monoclonal antibody specifically recogni zing cyclin D1 protein in various assays including immunohistochemistr y on frozen and paraffin sections. Using the DCS-6 antibody as a tool, we now show a characteristic cell cycle-dependent variation of the cy clin D1 protein in human cultured cells and report on the first immuno histochemical study of this G1 cyclin in a range of normal human tissu es and breast carcinomas. Analysis of normal tissues revealed generall y low levels of cyclin D1 protein, mainly restricted to the proliferat ive zones of some epithelial tissues, and the lack of its expression i n several human tissues including lymph nodes, spleen, and tonsils. In contrast, pronounced overexpression/nuclear accumulation of cyclin D1 was found in 37 per cent of cases in a series of 35 primary ductal ca rcinomas of the breast. We conclude that the DCS-6 antibody provides a potentially useful tool for the establishment of simple methods suita ble for verifying any diagnostic and/or prognostic value of this novel marker on large series of histological specimens and opens the way fo r biochemical, immunocytochemical, and immunohistochemical studies of the role played by cyclin D1 aberrations in human oncogenesis.