Interferon inducible antiviral MxA is inversely associated with prostate cancer and regulates cell cycle, invasion and Docetaxel induced apoptosis.
Interferon inducible antiviral MxA is inversely associated with prostate cancer and regulates cell cycle, invasion and Docetaxel induced apoptosis.
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DOI：
10.1002/pros.22912
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发表时间：
2015-02-15
期刊：
影响因子：
2.8
通讯作者：
Chaudhary, Jaideep
中科院分区：
文献类型：
--
作者：
Brown, Shanora G.;Knowell, Ashley E.;Hunt, Aisha;Patel, Divya;Bhosle, Sushma;Chaudhary, Jaideep
干扰素诱导的粘病毒（流感病毒）抗性A（MxA）被认为是干扰素诱导的抗病毒应答的关键介质。Mx蛋白含有典型的GTP结合基序，与发动蛋白家族的GTP酶具有很高的同源性。MxA与微管蛋白的强相互作用表明Mx蛋白可能参与有丝分裂。研究表明，MxA抑制肿瘤运动/转移和病毒诱导的细胞凋亡。然而，MxA表达与癌症之间的明确关联仍然未知。Meta分析显示MxA表达与前列腺癌（PCa）呈负相关。在这项研究中，我们证明了MxA在PCa中的表达及其对癌症表型的功能意义。免疫组化法检测前列腺癌组织中MxA蛋白的表达。MxA在DU 145和LNCaP PCa细胞系中分别被敲低（shMxA）或过表达（pMxA）。这些细胞系用于研究增殖、凋亡、侵袭、迁移和锚定非依赖性生长。在多西他赛治疗后，通过免疫细胞化学进行MxA与微管蛋白的共定位。MxA蛋白在PCa中的表达较正常组织明显降低。缺失MxA的DU 145细胞（DU 145 +chMxA）表现出显著的增殖增加，与CDKN 1A和B的表达降低相关。DU 145 +shMxA细胞中迁移增加、锚定非依赖性生长与MMP 13表达增加相关。微管蛋白的组织化也依赖于MxA的表达。微管蛋白聚合剂如多西他赛在促进缺乏MxA的细胞凋亡方面不太有效，这是由于微管蛋白组织的改变。LNCaP细胞（LNCaP+pMxA）中MxA表达的增加导致细胞周期停滞，这与CDKN 1A表达的增加有关。在LNCaP细胞中，双氢睾酮也下调MxA的表达。MxA表达与前列腺癌呈负相关。通过DHT下调LNCaP细胞中的MxA，表明MxA可能在疾病进展中起重要作用。MxA表达的缺失导致转移增加和对多西他赛的敏感性降低，表明MxA表达可以决定化疗治疗的结果。需要进一步的研究来充分确定雄激素受体-IFN途径在调节正常前列腺和前列腺癌中MxA表达中的相互作用。
The interferon inducible Myxovirus (influenza virus) resistance A (MxA) is considered as a key mediator of the interferon -induced antiviral response. Mx proteins contain the typical GTP-binding motif and show significant homology to dynamin family of GTPases. Strong interaction of MxA with tubulin suggests that Mx proteins could be involved in mitosis. Studies have shown that MxA inhibit tumor motility/metastasis and virus induced apoptosis. However the clear association between MxA expression and cancer remains unknown. Meta-analysis suggested that MxA expression was inversely correlated with prostate cancer (PCa). In this study we demonstrate the expression MxA in PCa and its functional significance on the cancer phenotype. The expression of MxA protein in prostate cancer was examined by immuno-histochemistry. MxA was knocked down (shMxA) or over-expressed (pMxA) in DU145 or LNCaP PCa cell lines respectively. These cell lines were used to study proliferation, apoptosis, invasion, migration and anchorage independent growth. Co-localization of MxA with tubulin was performed by immuno-cytochemistry following Docetaxel treatment. The expression of MxA protein was significantly decreased in PCa as compared to the normal tissues. DU145 cells lacking MxA (DU145+chMxA) showed significant increase in proliferation, associated with decreased expression of CDKN1A and B. Increased migration, anchorage independent growth in DU145+shMxA cells was associated with increased MMP13 expression. Tubulin organization was also dependent on MxA expression. Tubulin polymerizing agents such as Docetaxel was less effective in promoting apoptosis in cells lacking MxA due to altered tubulin organization. Gain of MxA expression in LNCaP cells (LNCaP+pMxA) resulted in cell cycle arrest that was associated with increased expression of CDKN1A. MxA expression was also down-regulated by dihydrotestosterone in LNCaP cells. MxA expression is inversely correlated with prostate cancer. Down-regulation of MxA in LNCaP cells by DHT suggests that MxA could play a significant role in disease progression. Loss of MxA expression results in increased metastasis and decreased sensitivity to Docetaxel suggesting that MxA expression could determine the outcome of chemo-therapeutic treatment. Additional studies will be required to fully establish the cross-talk between androgen receptor-IFN pathway in regulating MxA expression in the normal prostate and prostate cancer.
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影响因子：
11.2
作者：
Dunn, GP;Sheehan, KCF;Schreiber, RD
通讯作者：
Schreiber, RD
影响因子：
4.8
作者：
Accola, MA;Huang, B;McNiven, MA
通讯作者：
McNiven, MA
影响因子：
5.3
作者：
AEBI, M;FAH, J;STAEHELI, P
通讯作者：
STAEHELI, P
影响因子：
2.9
作者：
DIAZ, JF;ANDREU, JM
通讯作者：
ANDREU, JM
影响因子：
56.9
作者：
BROUTYBOYE, D;ZETTER, BR
通讯作者：
ZETTER, BR