文章：

MYB在正常细胞和癌细胞中起作用

MYB function in normal and cancer cells

原文发布日期：2008-07-01

DOI: 10.1038/nrc2439

类型: Review Article

开放获取: 否

要点：

1. The MYB oncogene is associated with leukaemogenesis in several species including humans. MYB can be activated by overexpression or inappropriate expression, structural alteration and/or genomic rearrangements.
2. MYB is clearly required in the bone marrow, colonic crypt and neurogenic niches as demonstrated when global or tissue-specific knockout mice were generated. Multiple cell types are affected and these contribute to the stem cell niches in these tissues.
3. MYB transcription is tightly regulated by attenuation sequences that reside in the first intron and mutations in this region in colorectal cancer correlate with elevated MYB expression, a characteristic of most colorectal cancers. In breast cancer oestrogen receptor-α (ERα) relieves the attenuation allowing elevated MYB expression, a characteristic of most ERα⁺ breast cancers.
4. Sub-optimal MYB function, either through protein changes or through heterozygous loss, compromises the ability to maintain tissue homeostasis when these tissues are subjected to stress. This might have clinical implications for treating patients with abnormal MYB function who would otherwise appear normal.
5. Over 80 cellular targets of the MYB transcription factor have been identified that partly, but incompletely, explain the importance of MYB in development, cell survival, proliferation and homeostasis. When MYB is overexpressed or inappropriately activated, some of these, and perhaps additional target genes, contribute to the transforming capacity of MYB.
6. Therapeutic interventions that target MYB in malignancy have been limited, but the observation that ERα⁺ breast cancer cells have elevated MYB indicates that targeting ERα-regulated gene expression might be efficacious. In addition, immunotherapy against MYB is now under investigation.

要点翻译：

1. MYB癌基因与包括人类在内的多种物种的白血病发生相关。MYB可通过过度表达或异常表达、结构改变和/或基因组重排而被激活。
2. 通过构建全身性或组织特异性基因敲除小鼠证实，MYB在骨髓、结肠隐窝和神经源性微环境中明确不可或缺。多种细胞类型受到影响，这些细胞共同构成了上述组织中的干细胞微环境。
3. MYB转录过程受位于第一内含子内的衰减序列严格调控，结直肠癌中该区域突变与MYB表达升高相关，这是大多数结直肠癌的典型特征。在乳腺癌中，雌激素受体α（ERα）可解除这种衰减机制导致MYB表达升高，这是大多数ERα阳性乳腺癌的典型特征。
4. 当这些组织处于应激状态时，因蛋白质改变或杂合性缺失导致的MYB功能次优，会损害维持组织稳态的能力。这对治疗MYB功能异常但表型正常的患者可能具有临床意义。
5. 目前已鉴定出80多个MYB转录因子的细胞靶标，这部分解释了MYB在发育、细胞存活、增殖和稳态中的重要性，但尚未完全阐明。当MYB过度表达或异常激活时，其中部分靶标及其他潜在靶基因共同促进了MYB的转化能力。
6. 针对恶性肿瘤中MYB的治疗干预目前有限，但ERα阳性乳腺癌细胞中MYB升高的现象表明，靶向ERα调控的基因表达可能具有疗效。此外，针对MYB的免疫疗法目前正在研究中。

英文摘要：

The transcription factor MYB has a key role as a regulator of stem and progenitor cells in the bone marrow, colonic crypts and a neurogenic region of the adult brain. It is in these compartments that a deficit in MYB activity leads to severe or lethal phenotypes. As was predicted from its leukaemogenicity in several animal species, MYB has now been identified as an oncogene that is involved in some human leukaemias. Moreover, recent evidence has strengthened the case that MYB is activated in colon and breast cancer: a block to MYB expression is overcome by mutation of the regulatory machinery in the former disease and by oestrogen receptor-α (ERα) in the latter.

摘要翻译： 

转录因子MYB在骨髓、结肠隐窝及成体脑内神经源性区域中，作为干细胞和祖细胞的关键调控因子发挥作用。正是在这些微环境中，MYB活性缺失会导致严重或致死性表型。正如其在多种动物模型中的致白血病作用所预示，MYB现已被确认为参与某些人类白血病的癌基因。此外，最新证据进一步证实MYB在结肠癌和乳腺癌中被激活：在前者，调控机制的突变解除了对MYB表达的抑制；在后者，雌激素受体α（ERα）则发挥了类似作用。

原文链接：

MYB function in normal and cancer cells