Cell：引发眼癌视网膜母细胞瘤的特异性细胞被识别

生物谷

    视网膜母细胞瘤是发生在婴幼儿视网膜的一种恶性肿瘤，也是眼球较为常见的恶性肿瘤之一。这种肿瘤恶性度很高，生长很快。绝大多数发生于5岁以下的儿童，多是单眼，大约25%是双眼发病。该病具有遗传性和家族性。视网膜母细胞瘤最初长在眼球最内层的视网膜上，从表面看不出任何迹象，孩子也不会有任何不舒服的感觉。当肿瘤发展影响视力时，可引起视力下降甚至视力丧失，这时孩子患病的眼睛可以出现内斜视或眼球震颤，黑眼球中央的瞳孔会散大，在瞳孔区可以看到眼底肿瘤反射出来的黄白色光，如同猫眼一般，医学上把这种没有视力，瞳孔开大并有黄光反射的现象叫做“黑朦猫眼”。

    80年代中期已将视网膜母细胞瘤基因（Rb）基因定位于13q14，并成功地从分子水平分离和克隆到Rb基因并对Rb基因及其蛋白产物的结构和生物学行为进行了深入研究，发现Rb基因的缺失或失活是肿瘤发生的关键，进而提出了肿瘤抑制基因的概念。

    近年来的研究发现视网膜母细胞瘤基因与细胞凋亡有关，White等认为Rb蛋白作用于细胞分化周期限的G1/S控制点，通过抑制转录延长因子E2F家族，对细胞周期循环起抑制作用。其过度表达既可使生长静止细胞合成DNA，又可导致细胞凋亡。Pans等研究发现Rb基因功能丧失引起的细胞凋亡可由p53介导。p53在转录水平激活WAF1（一种与p53相关的细胞周期循环基因）表达，从而抑制细胞周期循环。Nork等认为p53基因对视网膜母细胞瘤起一个管理作用。Kondon等证实在γ射线放疗治疗视网膜母细胞瘤中，瘤细胞的死亡导致了WAF1/CIP1基因的表达，通过白细胞介素1-β转化酶（interleukin-1  beta  converting  enzyme）的激活而引起凋亡。

原始出处:

Cell, Vol 131, 378-390, 19 October 2007

Article

Differentiated Horizontal Interneurons Clonally Expand to Form Metastatic Retinoblastoma in Mice

Itsuki Ajioka,1 Rodrigo A.P. Martins,1 Ildar T. Bayazitov,1 Stacy Donovan,1 Dianna A. Johnson,2 Sharon Frase,3 Samantha A. Cicero,1 Kelli Boyd,4 Stanislav S. Zakharenko,1 and Michael A. Dyer1,2,

1 Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA
2 Department of Ophthalmology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38105, USA
3 Integrated Microscopy Center, University of Memphis, Memphis, TN 38152, USA
4 Division of Pathology, Animal Resources Center, St. Jude Children's Research Hospital, Memphis, TN 38105, USA

Corresponding author
Michael A. Dyer
michael.dyer@stjude.org

Summary

During neurogenesis, the progression from a progenitor cell to a differentiated neuron is believed to be unidirectional and irreversible. The Rb family of proteins (Rb, p107, and p130) regulates cell-cycle exit and differentiation during retinogenesis. Rb and p130 are redundantly expressed in the neurons of the inner nuclear layer (INL) of the retina. We have found that in the adult Rb;p130-deficient retinae p107 compensation prevents ectopic proliferation of INL neurons. However, p107 is haploinsufficient in this process. Differentiated Rb^−/−;p107^+/−;p130^−/− horizontal interneurons re-entered the cell cycle, clonally expanded, and formed metastatic retinoblastoma. Horizontal cells were not affected in Rb^+/−;p107^−/−;p130^−/− or Rb^−/−;p107^−/−;p130^+/−, retinae suggesting that one copy of Rb or p130 was sufficient to prevent horizontal proliferation. We hereby report that differentiated neurons can proliferate and form cancer while maintaining their differentiated state including neurites and synaptic connections.