ABSTRACT
OBJECTIVE@#To investigate the expression of Dickkopf-1 and GATA-6 in laryngeal carcinoma and to discuss their relevance and the roles in carcinogenesis and development of laryngeal carcinoma.@*METHOD@#Immunohistochemical technique was used to detect the expression of Dickkopf-1 and GATA-6 protein in 48 tissues of larynge al carcinoma, 48 para-carcinoma tissues and 20 normal laryngeal mucosal tissues.@*RESULT@#(1) The expression of Dick kopf-1 protein in laryngeal cancer is significantly lower than in para-carcinoma tissues and normal laryngeal mucosa tissues (P < 0.05). (2) The expression of GATA-6 protein in laryngeal cancer is significantly higher than in para-carcinoma tissues and normal laryngeal mucosa tissues (P < 0.05). (3) The expression of Dickkopf-1 and GATA-6 protein in laryngeal cancer is correlated with lymph node metastasis, clinical stage, histological grade (P < 0.05). (4) The expression of Dickkopf-1 and GATA-6 are negatively correlated in laryngeal cancer.@*CONCLUSION@#The expression of Dickkopf-1 and GATA-6 may contribute to the carcinogenesis and development of laryngeal carcinoma.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , GATA6 Transcription Factor , Metabolism , Intercellular Signaling Peptides and Proteins , Metabolism , Laryngeal Neoplasms , Metabolism , PathologyABSTRACT
<p><b>OBJECTIVE</b>To study the role of sirtuin 1 (SIRT1) in Fas ligand (FasL) expression regulation during vascular lesion formation and to elucidate the potential mechanisms.</p><p><b>METHODS</b>SIRT1 and FasL protein levels were detected by Western blotting in either mouse arteries extract or the whole rat aortic vascular smooth muscle cell (VSMC) lysate. Smooth muscle cell (SMC)-specific human SIRT1 transgenic (Tg) C57BL/6 mice and their littermate wild-type (WT) controls underwent complete carotid artery ligation (ligation groups) or the ligation-excluded operation (sham groups). The carotid arteries were collected 1 day after operation. Reverse transcription-polymerase chain reaction was performed to detect the mRNA levels of SIRT1 and FasL. Luciferase reporter assays were performed to detect the effect of WT-SIRT1, a dominant-negative form of SIRT1 (SIRT1H363Y), and GATA-6 on the promoter activity of FasL. Flow cytometry assay was applied to measure the hypodiploid DNA content of VSMC so as to monitor cellular apoptosis.</p><p><b>RESULTS</b>SIRT1 was expressed in both rat aortic VSMCs and mouse arteries. Forced SIRT1 expression increased FasL expression both in injured mouse carotid arteries 1 day after ligation (P<0.001) and VSMCs treated with serum (P<0.05 at the transcriptional level, P<0.001 at the protein level). No notable apoptosis was observed. Furthermore, transcription factor GATA-6 increased the promoter activity of FasL (P<0.001). The induction of FasL promoter activity by GATA-6 was enhanced by WT-SIRT1 (P<0.001), while SIRT1H363Y significantly relieved the enhancing effect of WT-SIRT1 on GATA-6 (P<0.001).</p><p><b>CONCLUSIONS</b>Overexpression of SIRT1 up-regulates FasL expression in both flow-restricted mouse carotid arteries and serum-stimulated VSMCs. The transcription factor GATA-6 participates in the transcriptional regulation of FasL expression by SIRT1.</p>
Subject(s)
Animals , Male , Rats , Apoptosis , Carotid Arteries , Physiology , Fas Ligand Protein , Genetics , GATA6 Transcription Factor , Physiology , Muscle, Smooth, Vascular , Cell Biology , Metabolism , Myocytes, Smooth Muscle , Metabolism , RNA, Messenger , Rats, Sprague-Dawley , Sirtuin 1 , Physiology , Up-RegulationABSTRACT
The GATA family proteins are a group of zinc finger transcription factors that are expressed in human and mammalian animals and play an important role in mammalian organ morphogenesis, cell proliferation and sex differentiation. GATA-4 and GATA-6 have been identified in the ovaries and testes of humans, mice, pigs and chickens. GATA-4 contributes to fetal male gonadal development by regulating the genes that mediate Müllerian duct regression and the onset of testosterone production. GATA-4 and GATA-6 are localized in and regulate the function of the ovarian and testicular somatic cells of fetal mice, especially granulosa cells, thecal cells, Sertoli cells and Leydig cells. GATA-4 is also present in the germ cells of fetal and prepubertal mice.