Oxytocin induces the migration of prostate cancer cells: involvement of the Gi-coupled signaling pathway.
Oxytocin induces the migration of prostate cancer cells: involvement of the Gi-coupled signaling pathway.
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DOI：
10.1158/1541-7786.mcr-09-0329
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发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
Khan SA
中科院分区：
文献类型：
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作者：
Zhong M;Boseman ML;Millena AC;Khan SA
编码催产素（OXT）和抗利尿激素（AVP）及其同源受体的基因在正常和病变前列腺中的表达仅部分表征。利用逆转录和聚合酶链反应检测这些基因在正常前列腺上皮和基质细胞系、k-ras转化前列腺上皮细胞系和四种前列腺癌细胞系中的表达。分泌和细胞相关的OXT肽通过酶免疫分析法测定。OXT及其受体（OXTR）在8种前列腺细胞系中均有表达。除DU145细胞外，在所有前列腺上皮细胞系中均发现细胞相关的OXT肽。AVP及其同源受体（V1a受体和V2受体）均未在前列腺细胞系中表达。这些数据表明OXTR是OXT和AVP的主要靶点，并提示OXT可能是人类前列腺的自分泌/旁分泌调节因子。我们发现OXT能诱导PC3和PC3M的迁移，但不能诱导DU145前列腺癌细胞的迁移。OXT的作用不同于EGF诱导的前列腺癌细胞迁移，后者需要ERK 1/2和EGF受体激酶活性。当细胞用百日咳毒素预处理时，OXT而不是EGF对细胞迁移的影响被消除。用cAMP类似物8-Br-cAMP预处理不影响oxt诱导的细胞迁移，从而消除了百日咳毒素的非特异性作用。我们得出结论，OXTR介导的前列腺癌细胞迁移涉及gi依赖机制，并提示OXTR在前列腺癌转移中的作用。
Expression of genes that encode oxytocin (OXT) and vasopressin (AVP) and their cognate receptors in normal and diseased prostates are only partially characterized. Reverse transcription and polymerase chain reaction were used to examine the expression of these genes in normal prostate epithelial and stromal cell lines, k-ras transformed prostate epithelial cell line, and in four prostate cancer cell lines. Secreted and cell-associated OXT peptide was measured by an enzyme immunoassay. OXT and its receptor (OXTR) were expressed in all eight prostate cell lines. Cell-associated OXT peptide was also found in all prostate epithelial cell lines except in DU145 cells. Neither AVP nor its cognate receptors (V1a receptor and V2 receptor) were expressed in any prostate cell line examined. These data point to the OXTR as the primary target of OXT and AVP and suggest that OXT may be an autocrine/paracrine regulator in human prostate. We found that OXT induces migration of PC3 and PC3M, but not DU145 prostate cancer cells. The effect of OXT is distinct from the EGF-induced migration of prostate cancer cells, in which ERK 1/2 and EGF receptor kinase activities were required. When cells were pretreated with pertussis toxin, the effect of OXT, but not EGF, on cell migration was abolished. Pretreatment with the cAMP analogue, 8-Br-cAMP, did not affect the OXT-induced cell migration, which eliminated the non-specific effect of pertussis toxin. We conclude that a Gi-dependent mechanism is involved in OXTR-mediated migration of prostate cancer cells, and indicate a role of OXTR in prostate cancer metastasis.