Highly tumorigenic human androgen receptor-positive prostate cancer cells overexpress angiogenin
Highly tumorigenic human androgen receptor-positive prostate cancer cells overexpress angiogenin
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DOI：
10.1111/j.1349-7006.2007.00407.x
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发表时间：
2007-03-01
期刊：
影响因子：
5.7
通讯作者：
Ikeda, Daishiro
中科院分区：
文献类型：
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作者：
Kawada, Manabu;Inoue, Hiroyuki;Ikeda, Daishiro
我们最近建立了一个高致瘤性的细胞系，LNCaP-CR，来源于人雄激素依赖型前列腺癌LNCaP细胞。在本研究中，我们研究了导致LNCaP-CR细胞高致瘤性的基因。基因芯片分析和分泌因子蛋白质芯片分析表明，血管生成因子(Ang)是候选基因。逆转录聚合酶链式反应和免疫分析证实，与亲代LNCaP细胞相比，LNCaP-CR细胞表达高水平的Ang，但不表达血管内皮生长因子(VEGF)。我们还证明了另一种致癌雄激素受体阳性的前列腺癌细胞系22Rv1比血管内皮生长因子分泌更高水平的Ang。为了评价Ang在高致瘤性表型中的作用，我们将Ang基因导入LNCaP细胞以过表达Ang，并将Ang小干扰RNA表达载体导入LNCaP-CR细胞以下调Ang的表达。Ang在LNCaP细胞中的过表达不影响其体外生长，但显著增强体内的成瘤性和血管生成。相反，下调Ang在LNCaP-CR细胞中的表达也不会影响体外生长，但会显著降低成瘤性和血管生成。综上所述，Ang是导致LNCaP-CR细胞高致瘤性的基因之一。因此，我们的结果支持了Ang是一个有吸引力的肿瘤治疗靶点的观点，并表明LNCaP-CR细胞对于研究Ang的作用和针对Ang的实验性治疗方法是有用的。
We have recently established a highly tumorigenic cell line, LNCaP-CR, derived from human androgen-dependent prostate cancer LNCaP cells. In the present study, we examined the genes responsible for the high tumorigenicity of LNCaP-CR cells. The cDNA microarray analysis and protein array of secreted factors indicated angiogenin (ANG), an angiogenic factor, as a candidate gene. Reverse transcription polymerase chain reaction and immunoassay confirmed that LNCaP-CR cells expressed high levels of ANG but not vascular endothelial growth factor ( VEGF), compared with the parental LNCaP cells. We also proved that another tumorigenic androgen receptor-positive prostate cancer cell line, 22Rv1, secretes higher levels of ANG than VEGF. To assess the contribution of ANG to the highly tumorigenic phenotype, we transfected the ANG gene into LNCaP cells in order to overexpress ANG, and also transfected ANG small interfering RNA-expressing constructs into LNCaP-CR cells to downregulate ANG. Overexpression of ANG in LNCaP cells did not affect their growth in vitro, but it significantly enhanced tumorigenicity and angiogenesis in vivo. In contrast, knockdown of ANG expression in LNCaP-CR cells also did not affect the growth in vitro, but it led to a significant decrease in tumorigenicity and angiogenesis. Taken together, ANG is one of the genes responsible for the high tumorigenicity of LNCaP-CR cells. Thus, our results support the idea that ANG is an attractive target for cancer therapy and show that LNCaP-CR cells are useful for studying ANG action and experimental therapeutic approaches targeting ANG.