PURPOSE: hMena (ENAH), a cytoskeleton regulatory protein involved in the regulation of cell motility and adhesion, is overexpressed in breast cancer. The aim of this study was to define at what stage of breast carcinogenesis hMena is overexpressed and to correlate hMena overexpression with established prognostic factors in breast cancer, focusing on human epidermal growth factor receptor-2 (HER-2). EXPERIMENTAL DESIGN: hMena expression was assessed immunohistochemically in a prospective cohort of cases (n = 360) encompassing a highly representative spectrum of benign breast diseases associated with different risk of transformation, in situ, invasive, and metastatic tumors. Correlations with conventional pathologic and prognostic variables, such as proliferation index, hormonal receptor status, and HER-2 overexpression, were also evaluated. In vitro experiments were done to study the effect of neuregulin-1 and Herceptin treatments on hMena expression. RESULTS: hMena protein is undetectable in normal breast and is weakly expressed in a small percentage of low-risk benign diseases (9%), but displays a progressive and significant increase of positivity in benign lesions at higher risk of transformation (slightly increased risk 43%; moderate increased risk 67%), in in situ (72%), invasive (93%), and metastatic breast cancer (91%). A significant direct correlation with tumor size (P = 0.04), proliferation index (P < 0.0001), and HER-2 overexpression (P < 0.0001) and an inverse relationship with estrogen (P = 0.036) and progesterone receptors (P = 0.001) are found in invasive carcinomas. In vitro experiments show that neuregulin-1 up-regulates, whereas Herceptin down-regulates, hMena expression. CONCLUSIONS: Our data provide new insights into the relevance of actin-binding proteins in human breast carcinogenesis and indicate hMena overexpression as a surrogate indicator in breast disease management.
PURPOSE: hMena (ENAH), a cytoskeleton regulatory protein involved in the regulation of cell motility and adhesion, is overexpressed in breast cancer. The aim of this study was to define at what stage of breast carcinogenesis hMena is overexpressed and to correlate hMena overexpression with established prognostic factors in breast cancer, focusing on humanepidermal growth factor receptor-2 (HER-2). EXPERIMENTAL DESIGN: hMena expression was assessed immunohistochemically in a prospective cohort of cases (n = 360) encompassing a highly representative spectrum of benign breast diseases associated with different risk of transformation, in situ, invasive, and metastatic tumors. Correlations with conventional pathologic and prognostic variables, such as proliferation index, hormonal receptor status, and HER-2 overexpression, were also evaluated. In vitro experiments were done to study the effect of neuregulin-1 and Herceptin treatments on hMena expression. RESULTS: hMena protein is undetectable in normal breast and is weakly expressed in a small percentage of low-risk benign diseases (9%), but displays a progressive and significant increase of positivity in benign lesions at higher risk of transformation (slightly increased risk 43%; moderate increased risk 67%), in in situ (72%), invasive (93%), and metastatic breast cancer (91%). A significant direct correlation with tumor size (P = 0.04), proliferation index (P < 0.0001), and HER-2 overexpression (P < 0.0001) and an inverse relationship with estrogen (P = 0.036) and progesterone receptors (P = 0.001) are found in invasive carcinomas. In vitro experiments show that neuregulin-1 up-regulates, whereas Herceptin down-regulates, hMena expression. CONCLUSIONS: Our data provide new insights into the relevance of actin-binding proteins in humanbreast carcinogenesis and indicate hMena overexpression as a surrogate indicator in breast disease management.
Authors: Maria S Pino; Michele Balsamo; Francesca Di Modugno; Marcella Mottolese; Massimo Alessio; Elisa Melucci; Michele Milella; David J McConkey; Ulrike Philippar; Frank B Gertler; Pier Giorgio Natali; Paola Nisticò Journal: Clin Cancer Res Date: 2008-08-01 Impact factor: 12.531
Authors: Evanthia T Roussos; Michele Balsamo; Shannon K Alford; Jeffrey B Wyckoff; Bojana Gligorijevic; Yarong Wang; Maria Pozzuto; Robert Stobezki; Sumanta Goswami; Jeffrey E Segall; Douglas A Lauffenburger; Anne R Bresnick; Frank B Gertler; John S Condeelis Journal: J Cell Sci Date: 2011-07-01 Impact factor: 5.285
Authors: Evanthia T Roussos; Sumanta Goswami; Michele Balsamo; Yarong Wang; Robert Stobezki; Esther Adler; Brian D Robinson; Joan G Jones; Frank B Gertler; John S Condeelis; Maja H Oktay Journal: Clin Exp Metastasis Date: 2011-04-12 Impact factor: 5.150
Authors: Maja H Oktay; Frank B Gertler; Yi-Fang Liu; Thomas E Rohan; John S Condeelis; Joan G Jones Journal: J Histochem Cytochem Date: 2012-01-03 Impact factor: 2.479