2014年6月15日訊 /生物谷BIOON/--近日，伊利諾理工大學研究員Jialing Xiang最近發現更多關於Baxdelta2 (Baxdelta2是強大的腫瘤抑制基因，只有在變異的細胞中發現)導致癌細胞死亡的機制。研究論文刊登在Molecular Cancer Research雜誌上。他們的工作是由美國國立衛生研究院（NIH）的美國國家癌症研究所（NCI）資助。
某些遺傳微衛星不穩定的結腸腫瘤由於微衛星突變，往往失去抑癌Bax蛋白。但新研究發現這些結腸腫瘤會生成Bax的替代亞型Baxdelta2，Xiang發現Baxdelta2陽性細胞對化療藥物選擇性敏感。
這意味著，一直被認為Bax陰性的結腸直腸腫瘤能替代產生Baxdelta2，這對化療將是有益的。促凋亡蛋白Bax是在我們身體中腫瘤抑制基因之一。Bax蛋白的喪失都會對細胞「自殺」程序產生負面影響，會促進腫瘤的發展。生成Baxdelta2的能力意味著癌細胞可能重新觸發啟動凋亡過程。
Baxdelta2的發現將使我們更好地理解Bax蛋白陰性結腸癌，將幫助開發更有針對性的化療藥物治療。研究團隊正在研究試圖找出Baxdelta2的產生是如何被調控，並希望確定可以增強癌細胞生成Baxdelta2的藥物。（生物谷Bioon.com）
Baxdelta2 Promotes Apoptosis through Caspase-8 Activation in Microsatellite Unstable Colon Cancer
Honghong Zhang, Yuting Lin, Adriana Manas, Yu Zhao, Mitchell F. Denning, Li Ma, and Jialing Xiang.
Loss of apoptotic Bax due to microsatellite mutation contributes to tumor development and chemoresistance. Recently a Bax microsatellite mutation was uncovered in combination with a specific alternative splicing event that could generate a unique Bax isoform (Baxdelta2) in otherwise Bax-negative cells. Like the prototype Baxalpha, Baxdelta2 is a potent pro-apoptotic molecule. However, the pro-apoptotic mechanism and therapeutic implication of Baxdelta2 remain elusive. Here, the isolation and analysis of isogenic sub-cell lines are described that represent different Bax microsatellite statuses from colorectal cancer. Colon cancer cells harboring Bax microsatellite G7/G7 alleles are capable of producing low levels of endogenous Baxdelta2 transcripts and proteins. Interestingly, Baxdelta2-positive cells are selectively sensitive to a subgroup of chemotherapeutics compared with Baxdelta2-negative cells. Unlike other Bax isoforms, Baxdelta2 recruits caspase-8 into the proximity for activation, and the latter, in turn, activates caspase-3 and apoptosis independent of the mitochondrial pathway. These data suggest that the expression of Baxdelta2 may provide alternative apoptotic and chemotherapeutic advantages for Bax-negative tumors. Implications: "Bax-negative" colorectal tumors expressing a Bax isoform are sensitive to selective chemotherapeutics.