Genetics:Pla2g2a基因变异影响结肠癌的形成

2014-09-28 佚名 生物谷

由Kristi Neufeld博士领导的科学研究新发现,可能对癌症实验研究以及研究人员如何在小鼠体内测试抗癌药物、并最终对预防结肠癌产生潜在的重要影响。 Neufeld博士重点研究了一种可以防止结肠癌的基因——结肠腺瘤性息肉病基因(adenomatous polyposis coli,APC)。她的许多实验涉及到利用APC基因突变(这会导致结肠癌)小鼠来测试,观察是否会有针对该突变的新化合物。

由Kristi Neufeld博士领导的科学研究新发现,可能对癌症实验研究以及研究人员如何在小鼠体内测试抗癌药物、并最终对预防结肠癌产生潜在的重要影响。

Neufeld博士重点研究了一种可以防止结肠癌的基因——结肠腺瘤性息肉病基因(adenomatous polyposis coli,APC)。她的许多实验涉及到利用APC基因突变(这会导致结肠癌)小鼠来测试,观察是否会有针对该突变的新化合物。

几年前,Neufeld博士的研究小组发现,某些APC基因突变小鼠不会像其他APC基因突变鼠一样,发展患上结肠肿瘤。由于未患上结肠肿瘤的APC基因突变小鼠数量有限,因此未能利用其进行药物测试,Maged Zeineldin博士表示:由于不想让研究就此停止,他们继续探讨了结肠肿瘤发生频率意外减少的原因,并将报告发表在Genetics杂志上。

Neufeld博士的实验室发现了为什么有些APC基因突变小鼠发生有较少的肿瘤,研究发现这些小鼠Pla2g2a有基因修饰(基因变化),保护它们避免患上肿瘤。他们怀疑远交系无胸腺裸鼠(其通常用于抗肿瘤药物测试)也有Pla2g2a改变,后者可影响肿瘤的生长。

Neufeld博士说:我们想也许Pla2g2a变化可能会影响到其他致瘤性的研究。如果你将人类结肠癌细胞注入裸鼠体内,你不知道Pla2g2a改变的存在与否,因此也就不知道Pla2g2a改变会不会影响动物实验结果。

Neufeld博士现在将筛选老鼠Pla2g2a的多态性,并希望在此基础上进行其他癌症的研究,尤其是测试新的药物治疗,并弄清楚Pla2g2a遗传修饰如何改变实验的结果。

她解释说:我们认为这是非常重要的,因为如果有人注射癌细胞到裸鼠体内,裸鼠体内会生长肿瘤,然后给予一种化合物,看该化合物如何治疗癌症,但你不知道你看到的该化合物抗肿瘤结果是由于测试化合物真正有抗肿瘤效果,还是远交裸鼠基因差异所导致的。

Neufeld博士希望与其他实验室合作以确定是否Pla2g2a基因修饰会在人体产生类似的效果,以及Pla2g2a的过度表达是否可以预防人类结肠癌形成。这项新的研究发现有助于预防癌症或筛选出可能预测一个人患结肠癌风险的基因变异。也许医生有一天会像筛选BRCA或HER2基因一样,筛选Pla2g2a的变化,但研究人员首先必须弄明白Pla2g2a改变是否有助于防止肿瘤。

原始出处

Zeineldin M1, Jensen D2, Paranjape SR2, Parelkar NK3, Jokar I3, Vielhauer GA3, Neufeld KL4.Human Cancer Xenografts in Outbred Nude Mice Can Be Confounded by Polymorphisms in a Modifier of Tumorigenesis.Genetics. 2014 Jun 9

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    2015-06-14 canlab
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    2014-11-03 huperzia
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    2015-01-07 cy0324
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    2015-05-28 徐岩
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