RESUMO
BACKGROUND: Estrogen receptor (ER) signaling plays an important role in the development and functional differentiation of the breast and participates in the process of breast cancer. Activated ER can affect various aspects of the cell's behavior, including proliferation, via modulating the expression of many downstream target genes. Phosphorylation is one of the activation pathways of ER. However, the relationship between estrogen receptor phosphorylation sites and breast development and carcinogenesis is not clear. METHODS: Using Crisper-Cas9 gene editing technology, we constructed ER S309A mutant mice. Using carmine staining of the mammary gland of mice at different developmental stages, we examined the breast development of ER S309A mice. Using hematoxylin-eosin (HE) staining of vaginal smears of mice at the same time for 5 consecutive days, we measured the vaginal epithelial keratinocytes. RESULTS: We established ER S309A mutant mice and observed breast defects in ER S309A mice. In addition, we observed decreased reproductive ability, and estrous cycle disorder in ER S309A mice. The number of vaginal epithelial keratino-cytes in the estrous cycle of ER S309A mice was decreased. CONCLUSION: These results suggest that the phosphorylation site of ER at Serine 309 is important for ER function and breast development.
Assuntos
Serina , Animais , Feminino , Camundongos , Fosforilação , Serina/metabolismo , Humanos , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Mama/crescimento & desenvolvimento , Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/crescimento & desenvolvimento , MutaçãoRESUMO
BACKGROUND The aim of this study was to investigate the effects of metastasis-associated protein 1 (MTA1) deficiency during angiogenesis of pulmonary alveolar capillaries in mice and to determine the molecular mechanisms involved. MATERIAL AND METHODS The expressions of MTA1, CD34, vascular endothelial growth factor (VEGF), alpha smooth muscle actin (α-SMA), and HIF-1α were analyzed in the lungs of MTA1-knockout (KO) and wild-type mice at embryonic day 18.5 and 2 months by quantitative PCR, immunoblotting, and immunohistochemistry. The morphological changes were investigated during pulmonary alveolar capillary formation. The heart weight/body weight (HW/BW) ratio and the size of the right ventricular wall cardiomyocytes were also measured. Regulation of MTA1 on HIF-1α was determined in vitro. RESULTS MTA1 deficiency reduced the number of pulmonary alveolar capillaries compared to the wild-type mice. MTA1-KO mice exhibited a decreased expression of HIF-1α and VEGF in the lungs. The retarded growth of the MTA1-KO mice was also noticed during the first week after birth. Accordingly, MTA1 deficiency resulted in increased infant mortality. In surviving adult mice, MTA1 deficiency induced myocardial hypertrophy, highlighted by an increased heart weight/body weight ratio and larger cardiomyocytes. In cultured cells, HIF-1α and VEGF levels were significantly upregulated upon MTA1 overexpression, suggesting a close relationship between all 3 molecules. CONCLUSIONS MTA1 participates in the formation of pulmonary capillaries via stabilization of HIF-1α. This finding sheds new light on the function of MTA1 in lung development, opening new avenues for the diagnosis/treatment of related pulmonary diseases.
Assuntos
Alvéolos Pulmonares/irrigação sanguínea , Fatores de Transcrição/deficiência , Actinas/metabolismo , Animais , Antígenos CD34/metabolismo , Capilares/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imuno-Histoquímica , Camundongos , Camundongos Knockout , Miócitos Cardíacos/metabolismo , Neovascularização Fisiológica/fisiologia , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transativadores , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ativação Transcricional , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Diesel contamination poses a serious threat to ecosystem and human health. This study proposes a novel method for simultaneous diesel removal and recovery from heavily diesel-contaminated soil by washing based on three-liquid-phase equilibria of diesel+2-butoxyethanol+water. This work covers both theoretical-cum-experimental explorations. For this brand-new ternary three-liquid-phase system (TPS), Ternary-Gibbs and Fish-Shaped phase diagrams were constructed through the phase behavior investigation to provide theoretical support for diesel removal/recovery. As the experiment demonstrated, the removal efficiency was up to 87.5 % for the contaminated soil with diesel content of 226,723 mg/kg, and the recovery rate reached 73.8 %. In addition, the TPS could also be used continuously during the washing process while avoiding solution purification, and the detached diesel would automatically float into the top phase without complicated separation. The mechanism of diesel removal was determined as the surface "stripping" effect based on ultralow interfacial tension, and the enhanced process involved "stripping+dissolution". The treated soil contained almost negligible organic solvent residue and was therefore appropriate for plant cultivation. The recovered diesel exhibited less variation from commercial diesel in composition and properties, possessing a higher potential for reuse. Moreover, this study also provided key insights into the residual mechanisms of recalcitrant hydrocarbons in the soil.
Assuntos
Poluentes do Solo , Humanos , Poluentes do Solo/análise , Gasolina , Água , Ecossistema , Solo , Hidrocarbonetos , SolventesRESUMO
Epithelial-mesenchymal transition (EMT) is the phenotypic transition of epithelial cells to mesenchymal cells characterized by loss of epithelial markers, loss of intercellular adherence and acquirement of mesenchymal cell markers and increased locomotive ability. EMT is widely considered to be a gene regulated process necessary for cancer metastasis. Yet it is a highly controversial issue. We here propose that EMT is an environmentally induced cell behavior. It is the mimicry of their living environment. It is a survival strategy, a way of immune escape. We also propose here that the epithelial cell markers may functionally act as tumor antigens since in the mesenchymal surroundings there are no other structures bearing the same antigens as epithelial cells.