Ni Z, Lou W, Leman E S, Gao A C
Department of Pathology and Cancer Institute, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
Cancer Res. 2000 Mar 1;60(5):1225-8.
Overexpression of interleukin 6, a downstream target of the GBX2 homeobox gene, has been linked to the progression of prostate cancer. The Janus kinase-signal transducers and activators of transcription signaling pathway transmits interleukin 6-mediated signals from cell surface receptors to the target genes in the nucleus and is critical in mediating cellular growth and differentiation. We demonstrate that cells derived from both rat and human prostate cancers have constitutively activated Stat3, with Stat3 activation being correlated with malignant potential. Blockade of activated Stat3 by ectopic expression of a dominant-negative Stat3 in human prostate cancer cells significantly suppresses their growth in vitro and their tumorigenicity in vivo. Furthermore, the Janus kinase inhibitor, tyrphostin AG490, inhibited the constitutive activation of Stat3 and suppressed the growth of human prostate cancer cells. These results indicate that activation of Stat3 signaling is essential in the progression of prostate cancer cells and suggest that targeting Stat3 signaling may yield a potential therapeutic intervention for prostate cancer.
GBX2 同源盒基因的下游靶点白细胞介素 6 的过表达与前列腺癌的进展有关。Janus 激酶 - 信号转导子和转录激活子信号通路将白细胞介素 6 介导的信号从细胞表面受体传递至细胞核中的靶基因，在介导细胞生长和分化中起关键作用。我们证明，源自大鼠和人类前列腺癌的细胞均有组成性激活的 Stat3，且 Stat3 的激活与恶性潜能相关。在人类前列腺癌细胞中通过异位表达显性负性 Stat3 阻断激活的 Stat3，可显著抑制其体外生长及体内致瘤性。此外，Janus 激酶抑制剂 tyrphostin AG490 可抑制 Stat3 的组成性激活，并抑制人类前列腺癌细胞的生长。这些结果表明，Stat3 信号的激活在前列腺癌细胞进展中至关重要，并提示靶向 Stat3 信号可能为前列腺癌带来潜在的治疗干预手段。
