PKCδ and MAPK mediate G1 arrest induced by PMA in SKBR-3 breast cancer cells
PKCδ and MAPK mediate G1 arrest induced by PMA in SKBR-3 breast cancer cells
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DOI：
10.1016/j.bbrc.2004.12.070
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发表时间：
2005-02
影响因子：
3.1
通讯作者：
G. Yokoyama;T. Fujii;K. Tayama;H. Yamana;M. Kuwano;K. Shirouzu
中科院分区：
文献类型：
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作者：
G. Yokoyama;T. Fujii;K. Tayama;H. Yamana;M. Kuwano;K. Shirouzu
用佛波酯（PMA）处理乳腺癌细胞株SKBR-3，观察激活内源性蛋白激酶C（PKC）对细胞增殖和细胞周期的影响。这以浓度依赖性方式抑制细胞生长，导致G1期细胞明显停滞。GF 109203 X预处理可完全阻断PMA的抗增殖作用，PKCδ抑制剂rottlerin预处理可部分阻断PMA的抗增殖作用，而携带野生型PKCδ的腺病毒载体WTPKCδAdV感染SKBR-3细胞也可阻断PMA的抗增殖作用。用显性负性PKCδAdV感染细胞可阻断PMA对细胞生长的抑制作用。下游的PKC，PMA治疗抑制细胞外信号调节激酶丝裂原活化蛋白激酶磷酸化，上调c-jun NH 2-末端激酶磷酸化，并抑制视网膜母细胞瘤（Rb）磷酸化。这些结果表明PKC（主要是PKCδ）参与了PMA诱导的G1期阻滞，提示PKC可作为乳腺癌治疗的靶点。
The effects of activating endogenous protein kinase C (PKC) on cell proliferation and the cell cycle were investigated by treating the breast cancer cell line SKBR-3 with phorbol 12-myristate 13 acetate (PMA). This inhibited cell growth in a concentration-dependent manner, causing a marked arrest of cells in G1. Pre-treatment with GF109203X completely blocked the antiproliferative effect of PMA, and pre-treatment with the PKCδ inhibitor rottlerin partially blocked it. Infecting SKBR-3 cells with an adenovirus vector containing wild-type PKCδ, WTPKCδAdV, had similar effects on PMA. Infecting the cells with a dominant-negative PKCδAdV construct blocked the growth inhibition induced by PMA. Downstream of PKC, PMA treatment inhibited extracellular signal-regulated kinase mitogen-activated protein kinase phosphorylation, up-regulated c-jun NH2-terminal kinase phosphorylation, and inhibited retinoblastoma (Rb) phosphorylation. These results strongly implicated PKC (mainly PKCδ) in the G1arrest induced by PMA and suggested PKC as a target for breast cancer treatment.