Cyclin E2 is the predominant E-cyclin associated with NPAT in breast cancer cells.
BACKGROUND
The cyclin E oncogene activates CDK2 to drive cells from G1 to S phase of the cell cycle to commence DNA replication. It coordinates essential cellular functions with the cell cycle including histone biogenesis, splicing, centrosome duplication and origin firing for DNA replication. The two E-cyclins, E1 and E2, are assumed to act interchangeably in these functions. However recent reports have identified unique functions for cyclins E1 and E2 in different tissues, and particularly in breast cancer.


RESULTS
Cyclins E1 and E2 localise to distinct foci in breast cancer cells as well as co-localising within the cell. Both E-cyclins are found in complex with CDK2, at centrosomes and with the splicing machinery in nuclear speckles. However cyclin E2 uniquely co-localises with NPAT, the main activator of cell-cycle regulated histone transcription. Increased cyclin E2, but not cyclin E1, expression is associated with high expression of replication-dependent histones in breast cancers.


CONCLUSIONS
The preferential localisation of cyclin E1 or cyclin E2 to distinct foci indicates that each E-cyclin has unique roles. Cyclin E2 uniquely interacts with NPAT in breast cancer cells, and is associated with higher levels of histones in breast cancer. This could explain the unique correlations of high cyclin E2 expression with poor outcome and genomic instability in breast cancer.
The Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, Sydney, NSW Australia.
Samuel
S
Rogers
The Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, Sydney, NSW Australia ; St Vincent's Clinical School, Faculty of Medicine UNSW, Sydney, Australia.
Brian S
BS
Gloss
The Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, Sydney, NSW Australia.
Christine S
CS
Lee
The Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, Sydney, NSW Australia.
Claudio Marcelo
CM
Sergio
The Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, Sydney, NSW Australia ; St Vincent's Clinical School, Faculty of Medicine UNSW, Sydney, Australia.
Marcel E
ME
Dinger
Wolfson Wohl Cancer Research Centre, University of Glasgow, Garscube Estate, Glasgow, G61 1QH UK.
Elizabeth A
EA
Musgrove
The Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, Sydney, NSW Australia ; St Vincent's Clinical School, Faculty of Medicine UNSW, Sydney, Australia.
Andrew
A
Burgess
The Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, Sydney, NSW Australia ; St Vincent's Clinical School, Faculty of Medicine UNSW, Sydney, Australia.
Catherine Elizabeth
CE
Caldon
Breast cancer; CDK2; Cajal bodies; Centrosome; Cyclin E1; Cyclin E2; Histone Locus bodies (HLB); Histones; NPAT; Spliceosomes