Incadronate inhibits aminopeptidase N expression in prostatic PC-3 cells.
Incadronate inhibits aminopeptidase N expression in prostatic PC-3 cells.
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Incadronate 抑制前列腺 PC-3 细胞中氨肽酶 N 的表达。
DOI：
10.1016/j.canlet.2005.06.006
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发表时间：
2006
期刊：
影响因子：
9.7
通讯作者：
K. Hirano
中科院分区：
文献类型：
--
作者：
K. Iguchi;T. Nakano;S. Usui;K. Hirano
骨转移是晚期前列腺癌发病的重要原因。双膦酸盐被广泛用于治疗和预防骨质疏松症，但最近已观察到有效控制前列腺癌转移。由于已知氨肽酶N（AP-N）参与前列腺癌的转移，我们研究了双膦酸盐对AP-N表达的影响。Incadronate抑制PC-3细胞AP-N mRNA和蛋白表达。在用普伐他汀和其他含氮二膦酸盐处理的细胞中也观察到AP-N mRNA表达的抑制作用，其抑制类异戊二烯生物合成途径中的关键酶。与香叶基香叶基二磷酸（GGPP）共孵育可抑制因卡膦酸盐诱导的AP-N mRNA表达下降。此外，GGTI-286处理还导致AP-N mRNA表达降低。Incadronate和Pravastatin分别抑制了小G蛋白Rap 1从胞浆向胞膜的转运。上述结果表明，双膦酸盐引起的AP-N表达的降低与甲羟戊酸途径的抑制有关。
Bone metastasis is an important cause of morbidity in advanced prostate cancer. Bisphosphonates are widely used for the treatment and prevention of osteoporosis, but recently have been observed to be effective in controlling prostate cancer metastasis. Since aminopeptidase N (AP-N) is known to be involved in the metastasis of prostate cancer, we investigated the effect of bisphosphonate on AP-N expression. Incadronate induced inhibition of AP-N mRNA and protein expression in PC-3 cells. The inhibitory effect of AP-N mRNA expression was also observed in the cells treated with pravastatin and other nitrogen-containing bisphosphonates, which inhibit the key enzyme in the isoprenoid biosynthesis pathway. The decrease of AP-N mRNA expression induced by incadronate was inhibited by co-incubation with geranylgeranyl diphosphate (GGPP). Moreover, GGTI-286 treatment also resulted in reduced AP-N mRNA expression. The translocation of small G protein Rap1 from the cytosol to the membrane was inhibited by incadronate and pravastatin, respectively. These above results indicate that the decrease in AP-N expression elicited by bisphosphonate is related to the inhibition of the mevalonate pathway.
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影响因子：
11.2
作者：
Akira Sasaki;Brendan F. Boyce;B. Story;Kenneth R. Wright;Mark Chapman;Rogely Boyce;G. R. Mundy;Toshiyuki Yoneda
通讯作者：
Akira Sasaki;Brendan F. Boyce;B. Story;Kenneth R. Wright;Mark Chapman;Rogely Boyce;G. R. Mundy;Toshiyuki Yoneda
影响因子：
20.3
作者：
Bhagwat, SV;Lahdenranta, J;Shapiro, LH
通讯作者：
Shapiro, LH
影响因子：
11.2
作者：
R. Pasqualini;E. Koivunen;R. Kain;J. Lahdenranta;J. Lahdenranta;M. Sakamoto;A. Stryhn;R. Ashmun
通讯作者：
R. Pasqualini;E. Koivunen;R. Kain;J. Lahdenranta;J. Lahdenranta;M. Sakamoto;A. Stryhn;R. Ashmun
影响因子：
7.3
作者：
Szabo, CM;Matsumura, Y;Oldfield, E
通讯作者：
Oldfield, E