2013年11月19日訊 /生物谷BIOON/--澳大利亞阿德雷德大學科學家發現抑制淋巴瘤中起重要作用的基因。相關報導發表在近期的PNAS雜誌上。
caspase-2基因在細胞自我毀滅過程（即細胞凋亡）中起重要作用。該基因是由Sharad Kumar教授在二十年前發現的。二十年來Kumar教授抑制致力於研究細胞"生存還是死亡"的分子機制問題。
Kumar教授稱，細胞凋亡是有大量基因控制的，這些基因的異常往往會導致疾病。比如細胞不能進入凋亡過程就是癌症的標誌。
在本研究中Kumar領導的研究團隊發現caspase-2能夠抑制腫瘤形成。Kumar博士稱，染色體數目正常是細胞功能正常的前提， caspase-2通過某些未知的機制保證了染色體數目。而經常會發現癌細胞中的染色體數目異常。
Kumar博士補充道，該研究不僅為癌症發展機制的研究提供了新的證據，還揭示了caspase-2作為抑癌基因的作用，這是非常振奮人心的發現，我們將繼續研究該基因在癌症中的作用。（生物谷Bioon.com）
Loss of caspase-2 augments lymphomagenesis and enhances genomic instability in Atm-deficient mice
Joseph Puccini, Sonia Shalini, Anne K. Voss, Magtouf Gatei, Claire H. Wilson, Devendra K. Hiwase, Martin F. Lavin, Loretta Dorstyn, and Sharad Kumar
Caspase-2, the most evolutionarily conserved member of the caspase family, has been shown to be involved in apoptosis induced by various stimuli. Our recent work indicates that caspase-2 has putative functions in tumor suppression and protection against cellular stress. As such, the loss of caspase-2 enhances lymphomagenesis in Eμ-Myc transgenic mice, and caspase-2 KO (Casp2?/?) mice show characteristics of premature aging. However, the extent and specificity of caspase-2 function in tumor suppression is currently unclear. To further investigate this, ataxia telangiectasia mutated KO (Atm?/?) mice, which develop spontaneous thymic lymphomas, were used to generate Atm?/?Casp2?/? mice. Initial characterization revealed that caspase-2 deficiency enhanced growth retardation and caused synthetic perinatal lethality in Atm?/? mice. A comparison of tumor susceptibility demonstrated that Atm?/?Casp2?/? mice developed tumors with a dramatically increased incidence compared with Atm?/? mice. Atm?/?Casp2?/? tumor cells displayed an increased proliferative capacity and extensive aneuploidy that coincided with elevated oxidative damage. Furthermore, splenic and thymic T cells derived from premalignant Atm?/?Casp2?/? mice also showed increased levels of aneuploidy. These observations suggest that the tumor suppressor activity of caspase-2 is linked to its function in the maintenance of genomic stability and suppression of oxidative damage. Given that ATM and caspase-2 are important components of the DNA damage and antioxidant defense systems, which are essential for the maintenance of genomic stability, these proteins may synergistically function in tumor suppression by regulating these processes.