Interactions of STAP-2 with BRK and STAT3/5 in Breast Cancer Cells

Abstract

A number of molecular markers have recently been identified that may have prognostic value in breast cancer, and among the most notable of these are the estrogen receptor (ER) and the progesterone receptor (PR). ER/PR-positive breast cancer patients (60–80%) are hormone-responsive and therefore have a significantly better prognosis compared with ER/PR-negative patients (Clark and McGuire, 1983; Early Breast Cancer Trialists' Collaborative Group, 2005; Thorpe, 1988). However, approximately 50% of patients with advanced disease do not respond to endocrine therapy (Normanno et al., 2005). Another well-known prognostic marker is epidermal growth factor receptor-2 (ErbB2; also known as HER2), which is a member of the epidermal growth factor receptor (EGFR) family. In approximately 30% of human breast cancers, ErbB2 is present at levels significantly above those found in normal cells (Hynes and Stern, 1994; Stern, 2000; Yarden, 2001). Recent studies have indicated that ErbB2 plays important roles in malignant transformation and tumorigenesis (Hudziak et al., 1987; Slamon et al., 1987, 1989). Therefore, breast cancer tumors that involve large amounts of ErbB2 protein are correlated with poor clinical outcomes (Menard et al., 2001). Herceptin (also known as Trastuzumab), a humanized monoclonal antibody against the extracellular domain of ErbB2, is used to treat patients expressing high levels of ErbB2. Although Herceptin significantly decreases the rates of breast cancer recurrence and mortality (Piccart-Gebhart et al., 2005; Slamon et al., 2001; Ward et al., 2009), almost 50% of patients with the ErbB2amplified tumors do not respond to this treatment and develop resistance to the drug (Slamon et al., 2006). Conversely, tumors with neither hormone receptor expression nor ErbB2 amplification are classified as triple-negative (TN) tumors (Sorlie et al., 2003). TN tumors are an aggressive subtype of breast cancer that account for approximately 15% of breast cancer cases. The TN tumor shows a higher histologic grade, and a worse prognosis compared with that of hormone receptor-positive or ErbB2-positive tumors (Dent et al., 2007; Liedtke et al., 2008). Therapeutically, despite being highly chemosensitive, their progression-free time is generally short (Dent et al., 2007; Liedtke et al., 2008), and TN tumors develop resistance to endocrine therapy and Herceptin, illustrating the urgent need for novel therapeutic strategies. Recently, new potential therapeutic targets for this type of breast cancer have been discovered, including poly-(ADP-ribose)-polymerase 1