On the other hand, trastuzumab did not reduce the tumor growth of Ishikawa cells in xenograft mice (Fig. 6a). immunohistochemistry and RT-PCR to determine the protein and mRNA expression levels of EGFR. Western blot and WST-1 assays of EGFR ND-646 siRNA-transfected HEC-1A, KLE, and Ishikawa cells were used to evaluate the efficacy of erlotinib in tumor cell lines expressing different EGFR levels. Furthermore, HEC-1A and Ishikawa cells were implanted into athymic mice treated with either erlotinib or trastuzumab. == Results == At Gata2 our institution, 20. 9 % of endometrial cancer patients with low grade endometrioid histology have been diagnosed as stage III and IV. Immunohistochemical analysis and RT-PCR revealed the presence of significant EGFR and EGFR mRNA expression in low-grade endometrioid carcinoma in comparison with high-grade endometrioid carcinoma. In vitro study, WST-1 assay and Western blot analysis revealed that EGFR expression levels were correlated with tumor cell viability. Erlotinib reduced the proliferation of HEC-1A expressing high levels of EGFR, while trastuzumab showed similar effect in Ishikawa cells dominantly expressing human epidermal growth element receptor type2 (HER2). In vivo erlotinib decreased tumor growth in mice xenografted with HEC-1A cells, whereas this tumor-growth inhibition was not observed in trastuzumab-treated mice xenografted with Ishikawa cell. == Conclusions == EGF contributed to tumor proliferation in EC cell lines along with EGFR expression in vitro. Erlotinib also demonstrated anti-tumor effects in xenograft mice models. Our results suggest that erlotinib continues to have clinical usefulness in specific cases, after taking into consideration the EGFR expression levels. Keywords: Molecular targeted drug, Erlotinib, Endometrial cancer, EGFR == Background == Endometrial carcinoma (EC) is one of the most common gynecological malignant tumors in Japan; over 8000 women were diagnosed with it in 2012. There are two subtypes of endometrial carcinoma according to the clinico-pathological characteristics: type I EC and type II EC [1, 2]. Recent studies on gene signature in EC cells have reported numerous genetic disorders that initiate carcinogenesis: for instance, PTEN, which regulates normal cell function, is highly mutated in type I EC, whereas p53, which prevents genome mutation, ND-646 is altered by up to 8090 % in type II EC [3]. Type I EC accounts for about 80 % of EC, and is generally associated with better prognosis than type II EC since it is composed of low grade endometrioid histology with less intense characteristics and favorable prognosis [3]. However , the number of patients with advanced stage or recurrent low-grade tumors might not be negligible since type I EC comprises about 80 % of the newly diagnosed EC in Western Europe, North America, and Japan [3, 4]. After staging surgery, adjuvant therapy is considered based on the pathological risk factors, such as tumor grade, histological type, myometrial invasion, positive margin, lymphovascular space invasion, and positive node status [5]. Radiotherapy offers proved to reduce the risk of local recurrence, but no randomized study has shown benefit intended for overall survival [6, 7]. In the last decades, there has been emerging evidence suggesting that systemic cytotoxic chemotherapy may have favorable prognosis in advanced EC [8, 9]. Taxanes, platinum brokers, and anthracyclines have been utilized in advanced and recurrent EC patients, with response rates to these drugs ranging from 33 to 57 % [8, 1014]. Cytotoxic cancer therapy induces apoptosis in cancer cells by inhibiting microtubule function, protein function, or DNA synthesis. In contrast, molecular-targeted therapy is designed to interfere with specific molecules involved in cancer cell proliferation and metastasis. Recently, a better understanding of the molecular and genetic characteristics of EC has promoted clinical research that ND-646 focuses on angiogenesis and cellular signaling pathways involved in cancer development and progression. Epidermal growth factor receptor (EGFR) has been shown to be overexpressed in many human cancers, ND-646 including lung [15, 16], central nervous system [17], head and neck [18], bladder [19], pancreas [20], and breast [21]; and it correlates with poor prognosis [22]. EGFR expression.