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.