背景:SerpinB2在免疫和肿瘤细胞中高表达,并参与多种生物学功能,包括细胞存活和疾病进展的重塑。这项研究准备了SerpinB2缺陷的小鼠,并分析了差异表达的基因(DEG),以确定该蛋白质的丢失是否会延迟乳腺肿瘤的进展。
结果:总共305个DEG(75个上调,230个下调;>1.5倍差异,与PyMT肿瘤相比,在SB2-/-中鉴定出P<0.05)。DEGs主要参与与T细胞分化相关的免疫和炎症反应,IFN-γ生产,和基于61个富集GO术语的淋巴细胞趋化性,分层聚类,KEGG途径,和功能分组的注释网络。DEGs(Anxa3、Ccl17、Cxcl13、Cxcr3、IFN-γ、Nr4a1和Sema3a)在SB2-/-中至少注释了两个GO类别;通过qRT-PCR验证了PyMT肿瘤。
结论:SerpinB2缺乏改变了乳腺肿瘤中多个基因的表达,这可能会导致PyMT诱导的乳腺肿瘤进展延迟。
BACKGROUND: SerpinB2 is highly expressed in immune and tumor cells and is involved in multiple biological functions, including cell survival and remodeling for disease progression. This study prepared SerpinB2-deficient mice and analyzed the differentially expressed genes (DEGs) to determine if loss of this protein delays mammary tumor progression.
RESULTS: A total of 305 DEGs (75 upregulated and 230 downregulated; > 1.5-fold difference, P < 0.05) were identified in SB2-/-;PyMT tumors compared with PyMT tumors. The DEGs were mainly involved in immune and inflammatory responses related to T cell differentiation, IFN-γ production, and lymphocyte chemotaxis based on 61 enriched GO terms, hierarchical clustering, KEGG pathways, and a functionally grouped annotation network. The significantly changed DEGs (Anxa3, Ccl17, Cxcl13, Cxcr3, IFN-γ, Nr4a1, and Sema3a) annotated with at least two GO categories in SB2-/-;PyMT tumors was validated by qRT-PCR.
CONCLUSIONS: SerpinB2 deficiency alters the expression of multiple genes in mammary tumors, which might cause a delay in PyMT-induced mammary tumor progression.