simultaneous sirna targeting of src and downstream signaling molecules inhibit tumor formation and metastasis of a human model breast cancer cell line同时可以阻止针对src和下游信号分子抑制肿瘤的形成和转移人类乳腺癌细胞系模型.pdf

Simultaneous siRNA Targeting of Src and Downstream Signaling Molecules Inhibit Tumor Formation and Metastasis of a Human Model Breast Cancer Cell Line Jeffrey D. Bjorge1,2, Andy S. Pang1,2, Melanie Funnell1,2, Ke Yun Chen1,2, Roman Diaz3,4, Anthony M. Magliocco3,4, Donald J. Fujita1,2* 1 Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada, 2 Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada, 3 Department of Oncology, University of Calgary, Calgary, Alberta, Canada, 4 Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada Abstract Background: Src and signaling molecules downstream of Src, including signal transducer and activator of transcription 3 (Stat3) and cMyc, have been implicated in the development, maintenance and/or progression of several types of human cancers, including breast cancer. Here we report the ability of siRNA-mediated Src knock-down alone, and simultaneous knock-down of Src and Stat3 and/or cMyc to inhibit the neoplastic phenotype of a highly metastatic human model breast cancer cell line, MDA-MB-435S, a widely used model for breast cancer research. Methodology/Results: Src and its downstream signaling partners were specifically targeted and knocked-down using siRNA. Changes in the growth properties of the cultured cancer cells/tumors were documented using assays that included anchorage-dependent and -independent (in soft agar) cell growth, apoptosis, and both primary and metastatic tumor growth in the mouse tumor model. siRNA-mediated Src knock-down alone, and simultaneous knock-down of Src and Stat3 and/or cMyc inhibited the neoplastic phenotype of a highly metastatic human model breast cancer cell line, MDA-MB-435S. This knock-down resulted in reduced growth in monolayer and soft agar cultures, and a re