The possible correlation of Notch-1 and Notch-2 with clinical outcome and tumour clinicopathological parameters in human breast cancer.
The Notch-1 and Notch-2 receptors play crucial roles in cell fate determination through interaction with the Delta/Serrate/Lag-2 family of ligands. The function of Notch signalling in tumourigenesis is still unclear, however, reports have demonstrated unregulated Notch activity in a variety of human cancers. We quantified Notch-1 and Notch-2 expression, in association with clinical outcome, in tissue samples from breast cancer patients (normal specimens n=24, breast cancer specimens n=97). We used qualitative and quantitative RT-PCR analysis, along with immunohistochemical staining to examine Notch-1 and Notch-2 expression in association with the patients clinical parameters (median follow-up 72 months). Our results show that there are aberrant levels of Notch-1 and Notch-2 in breast cancer tissues compared with normal breast tissue. Examination of the breast cancer patients' clinicopathological parameters reported that a high level of Notch-1 may be associated with a poorer outlook for the breast cancer patient, while a high level of Notch-2 correlated to a higher chance of survival. Notch-1 and Notch-2 also appear to play crucial and contrasting roles in breast tumour differentiation. Notch-1 expression was low in grade 1 tumours and increased in poorly-differentiated tumours, whereas, Notch-2 expression was high in well-differentiated tumours and reduced in breast tumours with poor differentiation. Therefore, Notch-1 may possess tumour-promoting functions, while Notch-2 could play a tumour-suppressive role in human breast cancer. These results support the notion that suppression of Notch-1 activity may represent a novel therapeutic strategy.
Parr
C
C
Metastasis Research Group, University Department of Surgery, University of Wales College of Medicine, Cardiff CF4 4XN, UK. parrc@cf.ac.uk.
Watkins
G
G
Jiang
W G
WG
D001483:Base Sequence; D001940:Breast / Q000166:cytology / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016133:Polymerase Chain Reaction; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface / Q000235:genetics*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome
D017931:DNA Primers; C497761:NOTCH1 protein, human; C497764:NOTCH2 protein, human; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface; D014157:Transcription Factors