RelB/NF-κB links cell cycle transition and apoptosis to endometrioid adenocarcinoma tumorigenesis.

Dysfunction of nuclear factor-κB (NF-κB) signaling has been causally associated with numerous human malignancies. Although the NF-κB family of genes has been implicated in endometrial carcinogenesis, information regarding the involvement of central regulators of NF-κB signaling in human endometrial cancer (EC) is limited. Here, we investigated the specific roles of canonical and noncanonical NF-κB signaling in endometrial tumorigenesis. We found that NF-κB RelB protein, but not RelA, displayed high expression in EC samples and cell lines, with predominant elevation in endometrioid adenocarcinoma (EEC). Moreover, tumor cell-intrinsic RelB was responsible for the abundant levels of c-Myc, cyclin D1, Bcl-2 and Bcl-xL, which are key regulators of cell cycle transition, apoptosis and proliferation in EEC. In contrast, p27 expression was enhanced by RelB depletion. Thus, increased RelB in human EC is associated with enhanced EEC cell growth, leading to endometrial cell tumorigenicity. Our results reveal that regulatory RelB in noncanonical NF-κB signaling may serve as a therapeutic target to block EC initiation.

Cbx4 regulates the proliferation of thymic epithelial cells and thymus function.

Thymic epithelial cells (TECs) are the main component of the thymic stroma, which supports T-cell proliferation and repertoire selection. Here, we demonstrate that Cbx4, a Polycomb protein that is highly expressed in the thymic epithelium, has an essential and non-redundant role in thymic organogenesis. Targeted disruption of Cbx4 causes severe hypoplasia of the fetal thymus as a result of reduced thymocyte proliferation. Cell-specific deletion of Cbx4 shows that the compromised thymopoiesis is rooted in a defective epithelial compartment. Cbx4-deficient TECs exhibit impaired proliferative capacity, and the limited thymic epithelial architecture quickly deteriorates in postnatal mutant mice, leading to an almost complete blockade of T-cell development shortly after birth and markedly reduced peripheral T-cell populations in adult mice. Furthermore, we show that Cbx4 physically interacts and functionally correlates with p63, which is a transcriptional regulator that is proposed to be important for the maintenance of the stemness of epithelial progenitors. Together, these data establish Cbx4 as a crucial regulator for the generation and maintenance of the thymic epithelium and, hence, for thymocyte development.

[Study of HLA molecules and its associated genes expression in human ovarian cancer cells].

AIM: To explore the correlation between the expressions of HLA gene and its related gene, and expression of class II transactivator (CIITA) gene induced by IFN-gamma in human ovarian cells. METHODS: The expression of HLA molecule in the tumor cells was detected by Western blot, immunohistochemical staining and flow cytometry. The expressions of transporters associated with antigen processing (TAP), low molecular weight peptides (LMP), and CIITA genes were analyzed by RT-PCR. RESULTS: Abnormal expression rate of HLA class I molecule reached 45% in the 11 ovarian cancer cells. The expressed abnormalities of HLA class I molecule had relation to those of 4 genes (TAP1, TAP2, LMP2 and LMP7). Expression of HLA class II molecule was identical with that of CIITA gene in the ovarian cancer cells or other tumor cells. After IFN-gamma treatment, expressions of HLA class I and II molecule were increased in the cells of CIITA-expressing constitutively or inducibly, while no enhancement of HLA molecule expression manifested itself in the tumor cells of that CIITA was not yet expressed after IFN-gamma induction. CONCLUSION: Deletion of TAP and LMP gene expression in the ovarian cancer cells is an important factor causing abnormal expression of HLA class I molecule, suggesting that the CIITA gene has involved in the modulation of HLA classes I and II molecule expressions in the tumor cells.