IGF1R (Phospho-Tyr1165/Tyr1166) ELISA Kit

Purpose: Neuroendocrine lung tumors (NET) include typical carcinoids (TC), atypical carcinoids (AC), large cell NE carcinoma (LCNEC) and small-cell carcinoma (SCLC), with different clinicopathological profiles and relative grades of malignancy. Although differences between carcinoids and high grade carcinomas are recognized, precise differences and behavior of TC and AC have not been clearly defined. The aim of this study was to better define the differences in the clinical behavior of TC and AC, and to establish new prognostic factors of overall survival (OS), by determining the levels of genetic expression of IGF1R, ERCC1, Bax, p53, Bcl2 and Bcl2/Bax ratio. Methods: The histopathological diagnosis of 52 surgically resected pulmonary carcinoid tumors was made according to the WHO classification. Gene expressions were evaluated by quantitative real-time PCR. Results: The confirmed prognostic factors for overall survival (OS) were pTNM T (p<0.01) pTNM N (p<0.05), clinical stage (p<0.05), type of surgery (p<0.01) and histopathological (HP) tumor type (p<0.05). Bcl2 mRNA level and Bcl2/Bax ratio were found to have a potential for discrimination of the HP type of tumor (AC vs TC, Receiver Operating Characteristics (ROC) cut-off values 0.1451 and 0.3015, respectively), but without statistically significant impact on OS. Conclusions: In patients with NETs, smaller primary tumor, absence of positive lymph nodes, and TC type of tumor predicted longer OS. Type of resection has influence on OS. Bcl2 expression and Bcl2/Bax ratio might be valuable as independent diagnostic parametars in lung carcinoids. Therapeutic approaches using attenuation of Bcl2 or upregulation of Bax might prove useful in lung NETs.

Breast tumors display tremendous heterogeneity in part due to varying molecular alterations, divergent cells of origin, and differentiation. Understanding where and how this heterogeneity develops is likely important for effective breast cancer eradication. Insulin-like growth factor (IGF) signaling is critical for normal mammary gland development and function, and has an established role in tumor development and resistance to therapy. Here we demonstrate that constitutive activation of the IGF1 receptor (IGF1R) influences lineage differentiation during mammary tumorigenesis. Transgenic IGF1R constitutive activation promotes tumors with mixed histologies, multiple cell lineages and an expanded bi-progenitor population. In these tumors, IGF1R expands the luminal-progenitor population while influencing myoepithelial differentiation. Mammary gland transplantation with IGF1R-infected mammary epithelial cells (MECs) resulted in hyperplastic, highly differentiated outgrowths and attenuated reconstitution. Restricting IGF1R constitutive activation to luminal versus myoepithelial lineage-sorted MECs resulted in ductal reconstitutions co-expressing high IGF1R levels in the opposite lineage of origin. Using in vitro models, IGF1R constitutively activated MCF10A cells showed increased mammosphere formation and CD44+/CD24-population, which was dependent upon Snail and NF kappa B signaling. These results suggest that IGF1R expands luminal progenitor populations while also stimulating myoepithelial cell differentiation. This ability to influence lineage differentiation may promote heterogeneous mammary tumors, and have implications for clinical treatment.