Enhanced expression of SOS1 is detected in prostate cancer epithelial cells from African-American men
Enhanced expression of SOS1 is detected in prostate cancer epithelial cells from African-American men
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DOI：
10.3892/ijo_00000388
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发表时间：
2009-10-01
影响因子：
5.2
通讯作者：
Dritschilo, Anatoly
中科院分区：
文献类型：
--
作者：
Timofeeva, Olga A.;Zhang, Xueping;Dritschilo, Anatoly
与欧洲裔美国人(EA)男性相比，非洲裔美国人(AA)男性患前列腺癌的风险增加，治疗后死亡率增加。我们研究的目的是确定有可能使再障男性发生前列腺癌进展和转移的生物因素。为了确定AA男性的癌症特异性基因表达模式，我们建立了来自14名AA和13名EA男性的原代前列腺癌上皮细胞。高通量微阵列被用来比较两组在全球基因表达上的差异。定量逆转录聚合酶链式反应和免疫组织化学方法验证基因和蛋白的表达水平。RNAi敲除为前列腺癌细胞中已识别的基因提供了生物学意义的支持。Seven less Homolog I之子(SOSI)在AA男性来源的原代前列腺癌上皮细胞中高表达。PC3和DU145细胞中SOS I的缺失导致细胞的增殖、迁移和侵袭能力下降，至少部分是通过抑制细胞外信号调节激酶I和2。组织芯片分析前列腺癌中SOSI的表达与Gleason的肿瘤分级有关，这与前列腺癌的进展可能是一致的。对前列腺癌来源的上皮细胞的研究发现，SOS I是AA男性前列腺癌潜在的候选生物标记物和分子治疗靶点，这与AA男性前列腺癌侵袭性存在生物学基础的假设一致。
African-American (AA) men experience an increased risk of developing prostate cancers as well as increased mortality following treatment as compared to European-American (EA) men. The aim of our study was to identify biological factors with the potential to predispose AA men to prostate tumor progression and metastasis. To identify cancer-specific gene expression patterns in AA men, we established primary prostate cancer epithelial cells from 14 AA and 13 EA men. High-throughput microarrays were used to investigate differences in global gene expression comparing the two groups. Quantitative RT-PCR and immunohistochemistry validated mRNA and protein expression levels. RNAi knockdowns provided support for biological significance for the identified genes in prostate cancer cells. Son of sevenless homolog I (SOSI) was over-expressed in AA male-derived primary prostate cancer epithelial cells. Depletion of SOS I in PC3 and DU145 prostate cancer cells resulted in decreased capacities for cell proliferation, migration and invasion, at least partially through inhibition of extracellular signal-regulated kinase I and 2. Tissue microarray analyses of SOSI expression in prostate carcinomas correlated with Gleason's grades of tumors, consistent with a possible role in prostate cancer progression. Investigation of prostate cancer-derived epithelial cells has led to identification of SOS I as a potential candidate biomarker and molecular therapeutic target in prostate cancer in AA men, consistent with the hypothesis that a biological basis exists for prostate cancer aggressiveness in AA men.