title: 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.
abstract: 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-231(WASP+)) 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-231(WASP+ )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 therefore have significant clinical value in this condition.
authors.affiliation: Metastasis & Angiogenesis Research Group, Department of Surgery, Wales College of Medicine, Cardiff University, Cardiff CF14 4XN, UK. martinta1@cf.ac.uk
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Martin
authors.forename: Gordon
authors.initials: G
authors.lastname: Pereira
authors.forename: Gareth
authors.initials: G
authors.lastname: Watkins
authors.forename: Robert E
authors.initials: RE
authors.lastname: Mansel
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D014183:Transplantation, Heterologous; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism*
chemical_list: C495771:WASL protein, human; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal