ABUNDANCE AND SUBCELLULAR-LOCALIZATION OF CYCLIN D3 IN HUMAN TUMORS

The D-type cyclins are positive regulators of the G(1) phase of the ma mmalian cell cycle. Cyclins D1 or D2 are over-expressed in several typ es of cancer, transform rodent cells in culture and therefore harbor h allmarks of cellular proto-oncogenes. In contrast, no data on expressi on of cyclin D3 in tissues and tumours are presently available. We hav e raised monoclonal antibodies (MAbs) specific for cyclin D3 and exami ned abundance and subcellular localisation of this G(1) cyclin in a se ries of human cultured cell types and in 180 primary tumours of divers e histogenesis. Cyclin D3 localised predominantly in nuclei of normal and tumour cells both in culture and in situ, and a pronounced cell-to -cell variation of its abundance was reminiscent of cyclins D1 and D2. Immunohistochemical analysis of tumour and corresponding normal tissu es showed strong aberrant accumulation of cyclin D3 in a subset (about 10%) of breast carcinomas, whereas only weak-to-moderate expression w as found in colorectal, head and neck and uterine carcinomas, melanoma s and soft tissue sarcomas. The specificity of the immunohistochemical data was confirmed by immunoblotting analysis of tissue and tumour ly sates. Our results indicate that over-abundance of cyclin D3 is consid erably less frequent than that of cyclin D1, yet we identify subsets o f breast tumours, and potentially lymphomas, as candidate tumour types with elevated cyclin D3 expression. (C) 1996 Wiley-Liss, Inc.