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Breast cancer development is a complex pathobiological process involving sequential genetic alterations in normal epithelial cells that results in uncontrolled growth in a permissive microenvironment. Accordingly, physiologically relevant models of human breast cancer that recapitulate these events are needed to study cancer biology and evaluate therapeutic agents. Here, we report the generation and utilization of the human breast cancer in mouse (HIM) model, which is composed of genetically engineered primary human breast epithelial organoids and activated human breast stromal cells. By using this approach, we have defined key genetic events required to drive the development of human preneoplastic lesions as well as invasive adenocarcinomas that are histologically similar to those in patients. Tumor development in the HIM model proceeds through defined histological stages of hyperplasia, DCIS to invasive carcinoma. Moreover, HIM tumors display characteristic responses to targeted therapies, such as HER2 inhibitors, further validating the utility of these models in preclinical compound testing. The HIM model is an experimentally tractable human in vivo system that holds great potential for advancing our basic understanding of cancer biology and for the discovery and testing of targeted therapies. cancer model | human in mouse | tissue reconstitution

The telomerase ribonucleoprotein catalyzes the addition of new telomeres onto chromosome ends. A gene encoding a mammalian telomerase homolog called TP1 (telomerase-associated protein 1) was identified and cloned. TP1 exhibited extensive amino acid similarity to the Tetrahymena telomerase protein p80 and was shown to interact specifically with mammalian telomerase RNA. Antiserum to TP1 immunoprecipitated telomerase activity from cell extracts, suggesting that TP1 is associated with telomerase in vivo. The identification of TP1 suggests that telomerase-associated proteins are conserved from ciliates to humans., Telomerase is an unusual RNA-dependent DNA polymerase that uses an RNA Component to specify the addition of telomeric repeat sequences to chromosome ends (1). In humans the telomeric repeat is [...]

Targeting of the tsA58 mutation of simian virus 40 large tumor antigen to megakaryocytes results in the disturbance of megakaryocyte differentiation by the T antigen in the transgenic mice. Low platelets levels and large tumor antigen protein levels were seen in the affected cells. The morphological characteristics of the megakaryocytes and platelets in the thrombocytopenic mice are abnormal. A genetic model for megakaryocytic neoplasia and thrombocytopenia in the mice indicates the involvement of the retinoblastoma protein in megakaryocyte differentiation.