Abstract 1035: WAS/WASL interacting protein family, member 2 (WIPF2) expression in breast carcinomas
Authors: Daniel G. Tiezzi, Franklin F. Pimentel, Heriton MR Antonio, Renata Sicchieri, Daniela PC Tirapelli, Fabio M. Oliveira, Heitor RC Marana, Alfredo R. Silva, Maarten C. Bosland, Jurandyr M. Andrade, Carlos G. Carlotti Jr
Journal: Cancer Research (2011)

Abstract ERBB2 over-expression in breast carcinomas is associated with poor prognosis and early metastatic dissemination. The gene WIPF2 is located on the position q21.2 of the chromosome 17 between ERBB2 and TOP2A (17q21-q22) genes and encodes a WASP interacting protein (WIRE protein). It has been reported that this protein has a role in the WASP-mediated organization of the actin cytoskeleton. This protein is a potential link between the activated platelet-derived growth factor receptor and the actin polymerization machinery and its expression has never been evaluated in cancer tissues. The objectives of this investigation were the characterization of the levels of expression of WIPF2 gene in breast carcinomas and its correlation with EGFR 1 stimuli. Material and Methods: We studied the expression of WIRE protein in 87 ductal invasive carcinomas and WIPF2 gene in three breast cancer cell lines (Hb4a-C5.2, MCF7 and SKBR3). Breast cancer samples were mounted in a TMA block and the immunohistochemistry was performed to evaluate the expression of WIRE protein, estrogen receptor, progesterone receptor, HER-2 and Ki-67. The HER2, WIRE and KI-67 expression was further studied by using ImageScope software after digital image capture (Aperio). Tumors were classified according ER, PgR, HER2 and Ki-67 expression in luminal A or B, HER2 positive and basal-like subtypes. The WIPF2 and ERBB2 genes expression (real time RT-PCR) and WIRE protein (immunofluorescence) was analyzed in all cell lines before and after EGF treatment (40ng/µl for 12 and 72 hours). Results: We observed that WIRE protein is ubiquitously expressed in breast carcinomas. According to digital analysis, HER2 positive tumors have a higher expression of WIRE protein (p = 0.02). SKBR3 cell line (HER2 over expressed) has a significant 11 fold increase in WIPF2 gene expression comparing to MCF7. After EGF (EGFR 1 ligand) treatment, we observed a significant decrease in WIPF2 gene expression in SKBR3. Additionally, we observed a subcellular modification of WIRE protein, specially in SKBR3 cell line. The protein is usually dispersed into the cytoplasm. After EGF treatment, there is a reduction in its expression and the protein concentrate in endoplasmic reticulum (peri-nuclear). The decrease in WIPF2 gene expression and the subcellular protein modification is time dependent. They are more expressive after 72 hours of EGF exposure. Conclusion: WIRE protein is over-expressed in HER2 ductal breast carcinomas. EGF stimuli (EGFR1) changes its sub-cellular localization and reduces the WIPF2 gene expression in SKBR3 (HER2 positive) cell line. It is possible to infer that the expression of WIPF2 could be associated with ERFR signaling and the actin cytoskeleton motility. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1035. doi:10.1158/1538-7445.AM2011-1035