Zhang Li, Wang Jianghua, Wang Yongquan, Zhang Yiqun, Castro Patricia, Shao Longjiang, Sreekumar Arun, Putluri Nagireddy, Guha Nilanjan, Deepak Saligrama, Padmanaban Arunkumar, Creighton Chad J, Ittmann Michael
Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
Department of Pathology and Immunology and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
Cancer Res. 2016 Nov 1;76(21):6290-6298. doi: 10.1158/0008-5472.CAN-16-0087. Epub 2016 Aug 30.
Incidence and mortality rates for prostate cancer are higher in African-American (AA) men than in European-American (EA) men, but the biologic basis for this disparity is unclear. We carried out a detailed analysis of gene expression changes in prostate cancer compared with their matched benign tissues in a cohort of AA men and compared them with existing data from EA men. In this manner, we identified MNX1 as a novel oncogene upregulated to a relatively greater degree in prostate cancer from AA men. Androgen and AKT signaling play a central role in the pathogenesis of prostate cancer and we found that both of these signaling pathways increased MNX1 expression. MNX1 in turn upregulated lipid synthesis by stimulating expression of SREBP1 and fatty acid synthetase. Our results define MNX1 as a novel targetable oncogene increased in AA prostate cancer that is associated with aggressive disease. Cancer Res; 76(21); 6290-8. ©2016 AACR.
非裔美国(AA)男性前列腺癌的发病率和死亡率高于欧美裔(EA)男性,但这种差异的生物学基础尚不清楚。我们对一组AA男性前列腺癌与其匹配的良性组织中的基因表达变化进行了详细分析,并将其与EA男性的现有数据进行了比较。通过这种方式,我们确定MNX1是一种在AA男性前列腺癌中上调程度相对较高的新型癌基因。雄激素和AKT信号通路在前列腺癌的发病机制中起核心作用,我们发现这两种信号通路均增加了MNX1的表达。MNX1反过来通过刺激SREBP1和脂肪酸合成酶的表达上调脂质合成。我们的结果将MNX1定义为一种在AA前列腺癌中增加的新型可靶向癌基因,其与侵袭性疾病相关。《癌症研究》;76(21);6290 - 8。©2016美国癌症研究协会。