Laboratory of Experimental Pathology, GIGA-Cancer, University of Liège, Liège, Belgium; Laboratory of Virology and Hygiene & Microbiology, University Hassan II-Mohammedia, Mohammedia, Morocco.
Int J Exp Pathol. 2014 Aug;95(4):251-9. doi: 10.1111/iep.12077. Epub 2014 Apr 17.
Undifferentiated cell Transcription Factor 1 (UTF1) is a chromatin-bound protein involved in stem cell differentiation. It was initially reported to be restricted to stem cells or germinal tissues. However, recent work suggests that UTF1 is also expressed in somatic cells and that its expression may increase during carcinogenesis. To further clarify the expression profile of UTF1, we evaluated UTF1 expression levels immunohistochemically in eight normal human epithelia (from breast, prostate, endometrium, bladder, colon, oesophagus, lung and kidney) and their corresponding tumours as well as in several epithelial cell lines. We showed UTF1 staining in normal and tumour epithelial tissues, but with varying intensities according to the tissue location. In vitro analyses also revealed that UTF1 is expressed in somatic epithelial cell lines even in the absence of Oct4A and Sox2, its two main known regulators. The comparison of UTF1 levels in normal and tumoral tissues revealed significant overexpression in endometrial and prostatic adenocarcinomas, whereas lower intensity of the staining was observed in renal and colic tumours, suggesting a potential tissue-specific function of UTF1. Altogether, these results highlight a potential dual role for UTF1, acting either as an oncogene or as a tumour suppressor depending on the tissue. These findings also question its role as a specific marker for stem cells.
未分化细胞转录因子 1(UTF1)是一种结合在染色质上的蛋白,参与干细胞分化。最初报道称它仅局限于干细胞或生殖组织中。然而,最近的研究表明 UTF1 也在体细胞中表达,并且其表达可能在癌变过程中增加。为了进一步阐明 UTF1 的表达谱,我们通过免疫组织化学方法评估了 UTF1 在 8 种正常人类上皮组织(来自乳腺、前列腺、子宫内膜、膀胱、结肠、食管、肺和肾脏)及其相应肿瘤以及几种上皮细胞系中的表达水平。我们发现 UTF1 在正常和肿瘤上皮组织中均有染色,但根据组织位置的不同,其染色强度也不同。体外分析还表明,即使没有其两个主要已知调节因子 Oct4A 和 Sox2,UTF1 也在上皮细胞系中表达。UTF1 在正常和肿瘤组织中的水平比较表明,子宫内膜腺癌和前列腺腺癌中存在显著过表达,而在肾脏和结肠肿瘤中观察到染色强度较低,提示 UTF1 可能具有组织特异性功能。总之,这些结果强调了 UTF1 的潜在双重作用,根据组织的不同,它可以作为癌基因或肿瘤抑制因子发挥作用。这些发现也对其作为干细胞特异性标志物的作用提出了质疑。