Hedgehog Overexpression Is Associated with Stromal Interactions and Predicts for Poor Outcome in Breast Cancer
Sandra A O'Toole, Dorothy A Machalek, Robert F Shearer, Ewan KA Millar, Radhika Nair, Peter Schofield, Duncan McLeod, Caroline L Cooper, Catriona M McNeil, Andrea McFarland, Nguyen Akira, Christopher J Ormandy, Min Ru Qiu, Brian Rabinovich, Luciano G Martelotto, Vu Duc, Gregory E Hannigan, Elizabeth A Musgrove, Daniel Christ, Robert L Sutherland Show all
Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2011
Hedgehog (Hh) signaling plays an important role in several malignancies but its clinical significance in breast cancer is unclear. In a cohort of 279 patients with invasive ductal carcinoma of the breast, expression of Hh ligand was significantly associated with increased risk of metastasis, breast cancer-specific death, and a basal-like phenotype. A paracrine signature, encompassing high epithelial Hh ligand and high stromal Gli1, was an independent predictor for overall survival in multivariate analysis. In 2 independent histological progression series (n = 301), Hh expression increased with atypia. Hh ligand overexpression in a mouse model of basal breast cancer increased growth, induced ..View full abstract
Awarded by The Cancer Institute NSW
Awarded by National Health and Medical Research Council
Australia Breast Cancer Tissue Bank is generously supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW, and the National Breast Cancer Foundation. This work was supported by the following grants: the National Health and Medical Research Council (grant nos. 481378 (S. A. O'Toole), 427601 (R. L. Sutherland) and 535947 (S. A. O'Toole, A. Swarbrick, D.N. Watkins), the Cancer Institute NSW [grant nos. 08/ECF/1-12 (A. Swarbrick), 07/CRF/1-06 (S. A. O'Toole), and 07-CDF-1/28 (E. A. Musgrove)], the St Vincent's Clinic Foundation, the National Breast Cancer Foundation, the Australian Cancer Research Foundation, the RT Hall Trust, and the Petre Foundation.