Expressions and significances of TTF-1 and PTEN in early endometrial cancer.

OBJECTIVE: To analyze the expressions and significances of TTF-1 (Thyroid transcription factor-1) and PTEN (Phosphatase and tensin homolog) in early endometrial cancer. PATIENTS AND METHODS: 41 patients with endometrial cancer, 38 patients with proliferative endometrium and 13 patients with normal endometrium, were selected. The fluorescence quantitative PCR (polymerase chain reaction) was used to detect the expression levels of TFF-1 and PTEN mRNAs (Messenger ribonucleic acids) in the above three endometria, and their relations with clinical pathological characteristics were analyzed. The RT-PCR (reverse transcription-polymerase chain reaction) was employed to detect the expression levels of miR-135b, miR-125b and Snail mRNAs in the three endometria, and their correlations with the expressions of TTF-1 and PTEN mRNAs, were analyzed. RESULTS: The expression levels of TFF-1 and PTEN mRNAs in endometrial cancer tissues were significantly lower than those in the other two groups, while those in normal endometrium tissues were the highest, and the differences were statistically significant (p < 0.05). There were no significant differences in the menstruation status and the expression levels of TFF-1 and PTEN mRNAs between adenocarcinoma and squamous carcinoma (p > 0.05). With the increase of FIGO (International Federation of Gynecology and Obstetrics) stage and depth of invasion, as well as the metastasis of pelvic lymph nodes, the expression levels of TFF-1 and PTEN mRNAs were significantly decreased, and the differences were statistically significant (p < 0.05). The expression level of miR-135b mRNA in endometrial cancer was significantly higher than that in the other two groups, while that in normal endometrium was the lowest. The expression levels of miR-125b and Snail mRNAs were significantly lower than those in the other two groups, while those in normal endometrium were the highest; the differences were statistically significant (p < 0.05). Expression levels of TTF-1 and PTEN mRNAs were negatively correlated with the expression level of miR-135b mRNA, and positively associated with the expression levels of miR-125b and Snail mRNAs (p < 0.05). The results from the ROC (Receiver Operating Characteristic) model showed that, for the diagnosis of endometrial cancer with TTF-1 mRNA, the sensitivity was 86.5%, the specificity was 84.2%, the accuracy (area under curve - AUC) was 0.823, 95% CI (confidence intervals) = 0.762-0.921, p = 0.012. For the diagnosis of endometrial cancer with PTEN mRNA, the sensitivity was 85.3%, the specificity was 83.6%, the accuracy was 0.842, 95% CI = 0.785-0.936, p = 0.010. CONCLUSIONS: TTF-1 and PTEN can be used as molecular markers for the early diagnosis of endometrial cancer, which are closely related to clinical features and may affect tumor progression by regulating the proliferation activity of tumor cells.

Chronic restraint stress decreases the repair potential from mesenchymal stem cells on liver injury by inhibiting TGF-ß1 generation.

Chronic psychological stress has been demonstrated to play an important role in several severe diseases, but whether it affects disease therapy or not remains unclear. Mesenchymal stem cells (MSCs) have been demonstrated to have therapeutic potentials in treating tissue injury based on their multidifferentiation potential toward various cell types. We investigated the effect of chronic restraint stress on therapeutic potential of MSCs on carbon tetrachloride (CCl4)-induced liver injury in mice. CCl4-induced mice were injected with enhanced green fluorescent protein-MSCs, which was followed by chronic restraint stress administration. Corticosterone and RU486, a glucocorticoid receptor (GR) antagonist, were employed in vivo and in vitro, too. In the present study, we illustrated that MSCs could repair liver injury by differentiating into myofibroblasts (MFs) which contribute to fibrosis, whereas stress repressed differentiation of MSCs into MFs displayed by reducing α-smooth muscle actin (α-SMA, a solid marker of MFs) expression. Whereas RU486 could maintain the liver injury reduction and liver fibrosis increases induced by MSCs in stressed mice and block the decrease of α-SMA expression induced by stress. Furthermore, chronic stress inhibited MFs differentiation from MSCs by inhibiting transforming growth factor-ß1 (TGF-ß1)/Smads signaling pathway which is essential for MFs differentiation. Chronic stress reduced autocrine TGF-ß1 of MSCs, but not blunted activation of Smads. All these data suggested that corticosterone triggered by chronic stress impaired liver injury repair by MSCs through inhibiting TGF-ß1 expression which results in reduced MFs differentiation of MSCs.