6月12日,，Cancer Cell雜志報(bào)道了關(guān)于端粒失調(diào)與異常核型細(xì)胞產(chǎn)生及腫瘤發(fā)生之間關(guān)系的最新研究,。
人類亞四倍體核型腫瘤細(xì)胞被認(rèn)為起源于四倍體前體細(xì)胞,，但形成四倍體的起因尚不明了,。此前,，有研究證實(shí),，小鼠細(xì)胞核內(nèi)復(fù)制伴有持續(xù)的端粒功能失調(diào)和全基因組范圍的DNA損傷,。
本研究發(fā)現(xiàn),，在人類成纖維細(xì)胞和乳房上皮細(xì)胞端粒危機(jī)時，伴有核內(nèi)復(fù)制和有絲分裂失調(diào),。研究者還發(fā)現(xiàn)p53和Rb可抑制四倍體形成,。利用可誘導(dǎo)系統(tǒng)造成短期端粒破壞，研究者發(fā)現(xiàn)端粒驅(qū)動的四倍體形成加強(qiáng)了小鼠細(xì)胞的癌性轉(zhuǎn)化,。遺傳導(dǎo)致的腫瘤,，類似于人類實(shí)體瘤，演變出亞四倍體核型,。這些數(shù)據(jù)證實(shí),，特別短的端粒誘導(dǎo)了端粒驅(qū)動的四倍體形成。這在癌性損傷早期具有促進(jìn)腫瘤發(fā)生的潛能,。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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Telomere-Driven Tetraploidization Occurs in Human Cells Undergoing Crisis and Promotes Transformation of Mouse Cells
Teresa Davoli, Titia de Lange
Human cancers with a subtetraploid karyotype are thought to originate from tetraploid precursors, but the cause of tetraploidization is unknown. We previously documented endoreduplication in mouse cells with persistent telomere dysfunction or genome-wide DNA damage. We now report that endoreduplication and mitotic failure occur during telomere crisis in human fibroblasts and mammary epithelial cells and document the role of p53 and Rb in repressing tetraploidization. Using an inducible system to generate transient telomere damage, we show that telomere-driven tetraploidization enhances the tumorigenic transformation of mouse cells. Similar to human solid cancers, the resulting tumors evolved subtetraploid karyotypes. These data establish that telomere-driven tetraploidization is induced by critically short telomeres and has the potential to promote tumorigenesis in early cancerous lesions.
