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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

Martin, Tracey Amanda, Pereira, Gordon, Watkins, Gareth, Mansel, Robert Edward and Jiang, Wen Guo 2007. 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. Clinical & Experimental Metastasis 25 (2) , pp. 97-108. 10.1007/s10585-007-9120-8

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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-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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords: breast cancer, metastasis, nodal spread, N-WASP, prognosis
Publisher: Kluwer
ISSN: 0262-0898
Last Modified: 20 Oct 2017 09:41
URI: http://orca.cf.ac.uk/id/eprint/23271

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