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Adenomyosis is a common gynecological disorder defined by the presence of endometrial glands and stroma within the myometrium. Despite its frequent occurrence, the precise etiology of adenomyosis is still unknown, although it has often been associated with endometrioid adenocarcinoma. β-catenin abnormalities are common in endometrioid type endometrial carcinomas. The expression of the dominant stabilized β-catenin in the murine uterus (PRcre/+ Ctnnb1f(ex3)/+) resulted in endometrial glandular hyperplasia. In addition to the glandular hyperplasia phenotype, uteri of PRcre/+ Ctnnb1f(ex3)/+ mice exhibited an abnormal myometrial structure and proceed to develop adenomyosis. Ablation of Mig-6 in the murine uterus (PRcre/+ Mig-6f/f) leads to the development of endometrial hyperplasia and estrogen-induced endometrial cancer. Concomitant stabilization of β -catenin and ablation of Mig-6 dramatically accelerated the development of adenomyosis and glandular hyperplasia compared to stablizing β-catenin alone. The adenomyosis phenotype of ovariectomized Pffre/+ Ctnnb1f Citation Information: Clin Cancer Res 2010;16(14 Suppl):B23.

Two consecutive experiments were conducted for understanding immunity, stemness, and tumorigenesis of the embryonic stem cells (ESCs) in their allograft. In the first series of experiment, we evaluated whether co-injection of the stem cells with somatic cells could evade the immune response. Donor B6CBAF1 mouse ESCs were subcutaneously co-injected either alone or with ovarian stromal cells, fetal fibroblasts, or adult fibroblasts isolated from the recipient B6D2F1 mouse strain. ESCs by themselves induced teratomas (14%). However, when somatic cells were injected together, ESC-mediated teratoma formation significantly increased (33-75%). Especially, the highest rate of the teratoma formation was observed in ESCs and fetal fibroblasts co-injected recipient B6D2F1 mice (75%). Next, we derived ESC-like, cancer stem cells from the teratomas with enzymatic digestion and their differentiation potential was subsequently evaluated. Except for one cell line, other all cell lines showed a similar morphology to that of original ESCs and retained alkaline phosphatase activity, ESC-specific gene expression (Oct-4, Nanog, Cripto, and Rex-1), and Oct-4 protein expression regardless of their increased abnormality in chromosome number. Relative quantification of lineage-specific gene (Nestin, SMA, Desmin, and Krt8) expression of teratoma-derived cell lines showed the significant changes between the ESCs and the teratoma-derived, ESC-like cells derived from the cell co-injection. Variations in the type of co-injected cells led to lineage-specific changes, changes in gene expression in isolated colony-forming cells, and alterations in stem-cell-like cells derived from allografted tissues. In conclusion, our results suggest that cell-to-cell interaction regulates cellular immunity for implanted cells, which further affects tumorigenesis and stemness [Supported by a grant (SC-5160) from Stem Cell Research Center of the 21st Century Frontier Research Program awarded by Jeong-Mook Lim]. Jong-Heum Park and Seo-Jin Oh contributed equally to this work. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B25.