WNT5A Expression in Human Breast Cancer

Abstract

The Wnt family encodes secreted signaling molecules involved in cell adhesion and, by implication, cell growth. Wnt5a has been shown to behave as a putative oncogene and also as a tumour suppressor gene. This is a reflection of its role within a multi-step pathway and in the variety of ways in which its production can be stimulated or switched off. Wnt genes can be functionally separated into two classes; those that activate the canonical Wnt/beta-catenin pathway and those that activate the Wnt/Ca++ pathway. Wnt5a signals through frizzled receptors and, depending upon which frizzled receptor is present, may activate either pathway. Therefore the observed function of Wnt5a is entirely dependent upon its context, hence the confusion over its role in tumorigenesis. This study examines Wnt5a mRNA expression using RT-PCR in human breast cancer. Materials and Methods: One hundred and twenty malignant breast tumours and 33 normal breast tissues were analysed. The levels of transcription of Wnt5a were determined using real-time quantitative PCR. Levels of expression were analysed against staging, nodal involvement, grade, distant metastasis and survival over a 6-year follow-up period. Results: Levels of Wnt5a mRNA were lower in tumours than in normal tissue (mean values: 107 vs. 62.7). They fell further with increasing stage using the Nottingham Prognostic Index. This became statistically significant when NPI3 was compared to normal tissue (p=0.043, t-test). There was a trend towards lower levels of Wnt5a in those with progressive disease, however, this did not reach statistical significance. In patients with ER-negative disease, lower levels of Wnt5a were significantly associated with a worse clinical outcome (p=0.016). Conclusion: There is a trend for mRNA levels to be lower in cancerous tissue and lower still in those showing more aggressive behaviour. This is consistent with the hypothesis that Wnt5a is a tumour suppressor gene with potential clinical applications.