Mashanov Vladimir S, Zueva Olga R, Rojas-Catagena Carmencita, Garcia-Arraras Jose E
Department of Biology, University of Puerto Rico, PO Box 70377, San Juan, PR 00936-8377, USA.
BMC Dev Biol. 2010 Nov 29;10:117. doi: 10.1186/1471-213X-10-117.
The proper balance of cell division and cell death is of crucial importance for all kinds of developmental processes and for maintaining tissue homeostasis in mature tissues. Dysregulation of this balance often results in severe pathologies, such as cancer. There is a growing interest in understanding the factors that govern the interplay between cell death and proliferation under various conditions. Survivin and mortalin are genes that are known to be implicated in both mitosis and apoptosis and are often expressed in tumors.
The present study takes advantage of the ability of the sea cucumber Holothuria glaberrima Selenka, 1867 (Holothuroidea, Aspidochirota) to discard its viscera and completely regrow them. This visceral regeneration involves an extensive expression of survivin and mortalin transcripts in the gut mesothelium (the outer tissue layer of the digestive tube), which coincides in time with drastic de-differentiation and a burst in cell division and apoptosis. Double labeling experiments (in situ hybridization combined with TUNEL assay or with BrdU immunohistochemistry) suggest that both genes support cell proliferation, while survivin might also be involved in suppression of the programmed cell death.
Visceral regeneration in the sea cucumber H. glaberrima is accompanied by elevated levels of cell division and cell death, and, moreover, involves expression of pro-cancer genes, such as survivin and mortalin, which are known to support proliferation and inhibit apoptosis. Nevertheless, once regeneration is completed and the expression pattern of both genes returns to normal, the regrown digestive tube shows no anomalies. This strongly suggests that sea cucumbers must possess some robust cancer-suppression mechanisms that allow rapid re-growth of the adult tissues without leading to runaway tumor development.
细胞分裂与细胞死亡的适当平衡对于各种发育过程以及维持成熟组织中的组织稳态至关重要。这种平衡的失调常常导致严重的病理状况，如癌症。人们对了解在各种条件下控制细胞死亡与增殖之间相互作用的因素的兴趣日益浓厚。存活素和mortalin是已知与有丝分裂和细胞凋亡均有关联且常在肿瘤中表达的基因。
本研究利用了1867年的光滑海参（海参纲，楯手目）丢弃其内脏并使其完全再生的能力。这种内脏再生涉及存活素和mortalin转录本在肠间皮（消化管的外层组织）中的广泛表达，这与剧烈的去分化以及细胞分裂和凋亡的激增在时间上相吻合。双重标记实验（原位杂交结合TUNEL检测或BrdU免疫组织化学）表明这两个基因均支持细胞增殖，而存活素可能还参与了对程序性细胞死亡的抑制。
光滑海参的内脏再生伴随着细胞分裂和细胞死亡水平的升高，而且涉及促癌基因如存活素和mortalin的表达，已知这些基因支持增殖并抑制凋亡。然而，一旦再生完成且这两个基因的表达模式恢复正常，再生的消化管并无异常。这强烈表明海参必定拥有一些强大的癌症抑制机制，能够使成体组织快速再生而不会导致肿瘤的失控发展。
