p53是一種腫瘤抑制基因（gene）。在所有惡性腫瘤中,，50%以上會出現(xiàn)該基因的突變,。由這種基因編碼的蛋白質(zhì)（protein）是一種轉(zhuǎn)錄（transcription）因子，其控制著細胞周期的啟動,。該基因編碼一種分子量為53kDa的蛋白質(zhì),，p53基因的失活對腫瘤形成起重要作用。
腫瘤抑制基因p53參與DNA修復,、細胞周期阻滯和凋亡,，也參與抑制血管的形成過程，血管生成對促進腫瘤的發(fā)展非常有幫助,。p53基因表達12種不同的蛋白質(zhì)（亞型）,，包括TAp53（P53或p53α）、p53β和p53γ）和Δ133p53亞型（Δ133p53α,、Δ133p53β和Δ133p53γ）,。
近來研究證實Δ133p53α亞型調(diào)節(jié)p53的轉(zhuǎn)錄活性，在多種人類腫瘤類型中都過度表達,。然而,，Δ133p53α在腫瘤進展中的作用還在不斷探索中,。最新刊登在Oncogene雜志上的一項研究著重探討分析了Δ133p53對人腦膠質(zhì)瘤U87的血管生成和腫瘤生長的作用,。
研究人員收集去除Δ133p53后U87細胞的培養(yǎng)液，用培養(yǎng)液去孵育內(nèi)皮細胞,，結(jié)果發(fā)現(xiàn)該培養(yǎng)液不影響血管內(nèi)皮細胞在體外的增殖情況,，但能抑制內(nèi)皮細胞的遷移和血管腔形成。去除Δ133p53后U2OS骨肉瘤細胞的培養(yǎng)液也導致類似的血管生成抑制功效,。
此外,，在異位表達Δ133p53亞型U87的培養(yǎng)基中，研究人員證實了Δ133p53α和Δ133p53γ能刺激血管生成,，但Δ133p53β不具備刺激血管生成的功效,。使用U87膠質(zhì)母細胞瘤腫瘤雞絨毛尿囊膜血管生成模型和小鼠移植瘤模型證實去除Δ133p53亞型的U87腫瘤細胞，其血管生成和體內(nèi)生長都明顯受到抑制,。（生物谷：Bioon.com）
doi:10.1038/onc.2012.242
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The p53 isoform, Δ133p53α, stimulates angiogenesis and tumour progression
H Bernard, B Garmy-Susini, N Ainaoui, L Van Den Berghe, A Peurichard, S Javerzat, A Bikfalvi, D P Lane, J C Bourdon, and A-C Prats
The tumour suppressor p53, involved in DNA repair, cell cycle arrest and apoptosis, also inhibits blood vessel formation, that is, angiogenesis, a process strongly contributing to tumour development. The p53 gene expresses 12 different proteins (isoforms), including TAp53 (p53 (or p53α), p53β and p53γ) and Δ133p53 isoforms (Δ133p53α, Δ133p53β and Δ133p53γ). The Δ133p53α isoform was shown to modulate p53 transcriptional activity and is overexpressed in various human tumours. However, its role in tumour progression is still unexplored. In the present study, we examined the involvement of Δ133p53 isoforms in tumoural angiogenesis and tumour growth in the highly angiogenic human glioblastoma U87. Our data show that conditioned media from U87 cells depleted for Δ133p53 isoforms block endothelial cell migration and tubulogenesis without affecting endothelial cell proliferation in vitro. The Δ133p53 depletion in U2OS osteosarcoma cells resulted in a similar angiogenesis blockade. Furthermore, using conditioned media from U87 cells ectopically expressing each Δ133p53 isoform, we determined that Δ133p53α and Δ133p53γ but not Δ133p53β, stimulate angiogenesis. Our in vivo data using the chicken chorio-allantoic membrane and mice xenografts establish that angiogenesis and growth of glioblastoma U87 tumours are inhibited upon depletion of Δ133p53 isoforms. By TaqMan low-density array, we show that alteration of expression ratio of Δ133p53 and TAp53 isoforms differentially regulates angiogenic gene expression with Δ133p53 isoforms inducing pro-angiogenic gene expression and repressing anti-angiogenic gene expression.
