RESUMO
Tetraspanins are a family of transmembrane proteins that form membrane microdomains. They play important roles in migration, adhesion and other cellular processes. TspanC8, a subfamily of tetraspanins, was found to associate and promote ADAM10 trafficking and cell surface localization. One of its members, Tspan33, is expressed in activated B cells. Using RT-PCR and flow cytometry, we analysed the pattern of expression of Tspan33 in B cells from healthy donors. We found Tspan33 expression in early and late stages of B cell development. However, Tspan33 expression did not correlate with ADAM10 surface expression. We also found expression of Tspan33 early in the activation process. Given its predominant expression in activated B cells and in several lymphomas, but not in naive B cells, we hypothesize that Tspan33 could be a potential target for therapeutic purposes.
Assuntos
Proteína ADAM10/imunologia , Linfócitos B/imunologia , Memória Imunológica/imunologia , Tetraspaninas/imunologia , Proteína ADAM10/genética , Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígenos CD19/imunologia , Antígenos CD19/metabolismo , Antígenos de Diferenciação de Linfócitos T/imunologia , Antígenos de Diferenciação de Linfócitos T/metabolismo , Linfócitos B/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Citometria de Fluxo , Expressão Gênica/imunologia , Humanos , Lectinas Tipo C/imunologia , Lectinas Tipo C/metabolismo , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tetraspaninas/genética , Fatores de TempoRESUMO
Adenomyosis is a common gynaecological disorder characterized by the abnormal growth of endometrium into the myometrium and myometrial hypertrophy/hyperplasia. Uterine fibroids are benign neoplasms of the myometrium, and they represent a diagnostic pitfall for adenomyosis. In this study, we have used the genome-wide Affymetrix U133 Plus 2.0 microarray platform to compare the gene expression patterns of adenomyosis, uterine fibroids, normal endometrium and myometrium. Unsupervised principal component analysis (PCA) revealed that these four tissue types could be segregated from one another solely based on their gene expression profiles. Analysis of variance (ANOVA), followed by Tukey means separation test, significance analysis of microarrays (SAM) and 2-fold change threshold, identified 7415 probe sets as differentially expressed among the four groups of samples. Supervised cluster analysis based on these probe sets clustered adenomyosis most closely with endometrium and uterine fibroids with myometrium, consistent with the anatomic origin of these two diseases. The Tukey means separation post hoc testing found 2073 probe sets altered between adenomyosis and normal endometrium or myometrium, and 2327 probe sets altered in expression when comparing uterine fibroids with myometrium. Using Ingenuity Pathways Analysis (IPA), we found 9 highly significant functional networks in adenomyosis and 10 in uterine fibroids. Notably, the top network in both cases was associated with functions implicated in cancer and cell death. Finally, we compared the gene expression profiles of adenomyosis and uterine fibroids and identified 471 differentially expressed probe sets that may represent potential biomarkers for the differential diagnosis of these diseases.