2012年9月11日 訊 /生物谷BIOON/ --近日,，來(lái)自密歇根大學(xué)綜合癌癥研究中心和巴西圣保羅大學(xué)的研究者通過(guò)研究發(fā)現(xiàn)，兩個(gè)不同的遺傳突變可以合作從而誘導(dǎo)腎上腺癌發(fā)生,。這項(xiàng)研究為我們理解這種罕見(jiàn)的致死性的腎上腺癌提供了線(xiàn)索,，而且研究者希望為開(kāi)發(fā)特定的療法提供幫助。
在美國(guó)每年大約有600人診斷出腎上腺癌（adrenal cancer）,，而且其往往是在癌癥后期才能夠被診斷出來(lái),，這樣醫(yī)生幾乎沒(méi)有足夠時(shí)間治療這種癌癥，常常導(dǎo)致患者死亡,。
研究者Gary表示,，由于腎上腺癌非常罕見(jiàn)，因此發(fā)現(xiàn)足夠的病人,，并且提供足夠的樣品進(jìn)行研究顯得尤為困難,。我們的目標(biāo)是理解腫瘤的發(fā)生以及基因的突變以便我們可以開(kāi)發(fā)出治療措施來(lái)延長(zhǎng)患者的壽命,。
通過(guò)研究腎上腺組織樣品中的良性和惡性腫瘤，研究者發(fā)現(xiàn)良性腫瘤和惡性腫瘤在兩個(gè)遺傳通路上存在差別：β-連環(huán)蛋白（beta-catenin）和胰島素樣生長(zhǎng)因子2（IGF-2）,。β-連環(huán)蛋白在良性腫瘤中存在高比例的突變,，但是在良性腫瘤中IGF-2的上調(diào)卻很罕見(jiàn)。從另一個(gè)角度來(lái)講,，大部分的腎上腺癌都表現(xiàn)出IGF-2的上調(diào),，相比僅僅有IGF-2上調(diào)的腫瘤來(lái)說(shuō)，β-連環(huán)蛋白的突變的腫瘤和重病或者高死亡率直接相關(guān),。
研究者通過(guò)在腎上腺癌小鼠模型中誘發(fā)β-連環(huán)蛋白和IGF-2的單一突變或者雙突變,，結(jié)果發(fā)現(xiàn)，小鼠僅僅在雙突變的時(shí)候可以發(fā)展成為癌癥,。相關(guān)研究成果刊登在了近日的國(guó)際雜志the American Journal of Pathology上,。
下一步研究者希望通過(guò)阻擋β-連環(huán)蛋白和IGF-2通路來(lái)開(kāi)發(fā)出潛在的腎上腺癌療法。研究者表示,，促使癌癥的原因遠(yuǎn)遠(yuǎn)大于我們所發(fā)現(xiàn)的特殊基因,，越來(lái)越多的遺傳方法稱(chēng)為了新型的癌癥療法，因此未來(lái)的癌癥療法將很有可能是很多方法聯(lián)合起來(lái)來(lái)發(fā)揮作用的,。（生物谷Bioon.com）
編譯自：Two Gene Mutations Drive Adrenal Cancer
doi:10.1016/j.ajpath.2012.05.026
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PMID:
Progression to Adrenocortical Tumorigenesis in Mice and Humans through Insulin-Like Growth Factor 2 and β-Catenin
Joanne H. Heaton⁎, Michelle A. Wood⁎, Alex C. Kim⁎, Lorena O. Lima†, Ferdous M. Barlaskar⁎, Madson Q. Almeida†, Maria C.B.V. Fragoso†, Rork Kuick‡, Antonio M. Lerario†, Derek P. Simon⁎, Ibere C. Soares†, Elisabeth Starnes⁎, Dafydd G. Thomas§, Ana C. Latronico†, Thomas J. Giordano⁎, ‡, §, Gary D. Hammer⁎, ‡
Dysregulation of the WNT and insulin-like growth factor 2 (IGF2) signaling pathways has been implicated in sporadic and syndromic forms of adrenocortical carcinoma (ACC). Abnormal β-catenin staining and CTNNB1 mutations are reported to be common in both adrenocortical adenoma and ACC, whereas elevated IGF2 expression is associated primarily with ACC. To better understand the contribution of these pathways in the tumorigenesis of ACC, we examined clinicopathological and molecular data and used mouse models. Evaluation of adrenal tumors from 118 adult patients demonstrated an increase in CTNNB1 mutations and abnormal β-catenin accumulation in both adrenocortical adenoma and ACC. In ACC, these features were adversely associated with survival. Mice with stabilized β-catenin exhibited a temporal progression of increased adrenocortical hyperplasia, with subsequent microscopic and macroscopic adenoma formation. Elevated Igf2 expression alone did not cause hyperplasia. With the combination of stabilized β-catenin and elevated Igf2 expression, adrenal glands were larger, displayed earlier onset of hyperplasia, and developed more frequent macroscopic adenomas (as well as one carcinoma). Our results are consistent with a model in which dysregulation of one pathway may result in adrenal hyperplasia, but accumulation of a second or multiple alterations is necessary for tumorigenesis.
