Specific amino acid dependency regulates invasiveness and viability of androgen-independent prostate cancer cells
Specific amino acid dependency regulates invasiveness and viability of androgen-independent prostate cancer cells
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DOI：
10.1207/s15327914nc4501_8
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发表时间：
2003-01-01
影响因子：
2.9
通讯作者：
Meadows, GG
中科院分区：
文献类型：
--
作者：
Fu, YM;Yu, ZX;Meadows, GG
雄激素非依赖性前列腺癌对治疗有抗性，并且通常是转移性的。在这里，我们研究了剥夺酪氨酸和苯丙氨酸（Tyr/Phe），谷氨酰胺（Gln），或蛋氨酸（Met），在体外对人DU 145和PC 3雄激素非依赖性前列腺癌细胞，和非致瘤性人婴儿包皮成纤维细胞和人前列腺上皮细胞的影响。氨基酸剥夺同样抑制DU 145和PC 3细胞的生长，使细胞周期停滞在G 0/G1 Met和Tyr/Phe剥夺诱导DU 145细胞凋亡，但仅Met剥夺诱导PC 3细胞凋亡。正常细胞的生长受到抑制，但没有凋亡诱导的氨基酸剥夺。Tyr/Phe剥夺抑制DU 145中粘着斑激酶（FAK）和细胞外调节激酶（ERK）的表达和磷酸化，但不抑制PC 3或正常细胞。Met剥夺抑制PC 3中FAK和ERK的磷酸化，但不抑制蛋白表达。因此，氨基酸限制性酶切诱导的DU 145和PC 3细胞凋亡是FAK和ERK依赖性的。Tyr/Phe和Met剥夺抑制DU 145和PC 3的侵袭，而Gln剥夺仅抑制DU 145的侵袭。这表明侵袭的抑制不依赖于凋亡的诱导。DU 145中Tyr/Phe限制和PC 3中Met限制对侵袭的抑制与对FAK/ERK信号传导的抑制一致。PC 3中Tyr/Phe限制和DU 145中Gln限制的抑制与FAK/ERK的抑制无关。这表明FAK/ERK依赖性和非依赖性途径受到特定氨基酸限制的调节。这项研究显示了特定氨基酸限制治疗前列腺癌的潜力。
Androgen-independent prostate cancer is resistant to therapy and is often metastatic. Here we studied the effect of deprivation of tyrosine and phenylalanine (Tyr/Phe), glutamine (Gln), or methionine (Met), in vitro on human DU145 and PC3 androgen-independent prostate cancer cells, and on nontumorigenic human infant foreskin fibroblasts and human prostate epithelial cells. Deprivation of the amino acids similarly inhibited growth of DU145 and PC3 cells, arresting the cell cycle at G0/G1 Met and Tyr/Phe deprivation induces apoptosis in DU145, but only Met deprivation induces apoptosis in PC3 cells. The growth of normal cells is inhibited, but no apoptosis is induced by amino acid deprivation. Tyr/Phe deprivation inhibits expression and phosphorylation of focal adhesion kinase (FAK) and extracellular-regulated kinase (ERK) in DU145 but not PC3 or normal cells. Met deprivation inhibits phosphorylation but not protein expression of FAK and ERK in PC3. Therefore, apoptosis of DU145 and PC3 cells by amino acid restriction is FAK and ERK dependent. Tyr/Phe and Met deprivation inhibits invasion of DU145 and PC3, but Gln deprivation only inhibits invasion of DU145 cells. This indicates that the inhibition of invasion is not dependent on induction of apoptosis. The inhibition of invasion by Tyr/Phe restriction in DU145 and Met restriction in PC3 is consistent with the inhibition on FAK/ERK signaling. The inhibition of Tyr/Phe restriction in PC3 and Gln restriction in DU145 is not associated with inhibition of FAK/ERK. This indicates that FAK/ERK-dependent and independent pathways are modulated by specific amino acid restriction. This study shows the potential for specific amino acid restriction to treat prostate cancer.