N-WASP is a putative tumour suppressor in breast cancer cells, in vitro and in vivo, and is associated with clinical outcome in patients with breast cancer
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- Martin, T.A., Pereira, G., Watkins, G. et al. Clin Exp Metastasis (2008) 25: 97. doi:10.1007/s10585-007-9120-8
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N-WASP is a key regulator of cell migration and actin polymerisation. We examined the correlation of N-WASP, with human breast cancer, in vitro, in vivo and in clinical breast cancer tissue. Immunohistochemical study of frozen sectioned human breast mammary tissues (n = 124) revealed that mammary epithelial cells stained positively for N-WASP and that cancer cells in tumour tissues stained very weakly. Quantitative RT-PCR revealed that breast cancer tissues had significantly lower levels of N-WASP compared with normal background mammary tissues (0.83 ± 0.3 vs 13.6 ± 13, P = 0.03). Although no significantly correlation was found with tumour grade and TNM staging, lower levels of transcript were seen to correlate with clinical outcome following a ten year follow up. Thus tumours from patients with predicted poor prognosis had significantly lower levels than from those with good prognosis (0.098 ± 0.14 vs 1.14 ± 0.56, P = 0.05). Patients with metastatic disease/died of breast cancer had significantly lower levels of N-WASP compared to those remaining disease free (0.04 ± 0.02 and 0.47 ± 0.3, vs 0.79 ± 0.44, P = 0.01 and P < 0.05 respectively). During in vitro experiments, MDA-MB-231 cells stably transfected with N-WASP (MDA-MB-231WASP+) exhibited a significantly reduced in vitro invasiveness and motility compared with control and wild type cells (P < 0.0001), had increased adhesiveness (P = 0.05) and moreover MDA-MB-231WASP+ exhibited reduced in vivo growth (P = 0.002). The motogen HGF (50 ng/ml) caused a relocation of N-WASP to the cell periphery in a temporal and spatial response. It is concluded that N-WASP, a member of the N-WASP family may act as a tumour progression suppressor in human breast cancer and may thereforee have significant clinical value in this condition.