STAT3 mRNA and protein expression in colorectal cancer:: effects on STAT3-inducible targets linked to cell survival and proliferation
STAT3 mRNA and protein expression in colorectal cancer:: effects on STAT3-inducible targets linked to cell survival and proliferation
复制标题
DOI：
10.1136/jcp.2005.035113
复制
发表时间：
2007-02-01
影响因子：
3.4
通讯作者：
Werner, Martin
中科院分区：
文献类型：
--
作者：
Lassmann, Silke;Schuster, Ingrid;Werner, Martin
目的：评估结直肠癌 (CRC) 中信号转导子和转录激活子 (STAT) 3 的 mRNA 和蛋白表达，并确定 STAT3 活性与 STAT3 诱导靶标细胞周期蛋白 D1、生存素、Bcl-xl 和 Mcl-1 的关联。 材料和方法：对正常结肠上皮和侵袭性 CRC (n = 32) 的连续切片进行匹配，进行定量逆转录酶分析针对 STAT3、细胞周期蛋白 D1、生存素、Bcl-xl 和 Mcl-1 的聚合酶链反应以及免疫组织化学。对于 STAT3 免疫组织化学，使用了识别未磷酸化 (UP-) 和磷酸化 (tyr705，P-) STAT3 的两种抗体。 Ki-67（MIB-1）染色作为增殖标志物。 结果：与正常结肠上皮相比，癌中UP-STAT3和P-STAT3（p = 0.023和0.006）蛋白表达及其相关靶标cyclin D1、survivin和Bcl-xl的表达显着增加（均p < 0.001）。在癌症中，STAT3 (p = 0.019) 和 Bcl-xl (p = 0.001) mRNA 与淋巴结状态相关。此外，核 P-STAT3 蛋白表达（活性状态）与其靶基因 Bcl-xl (p = 0.038) 和 survivin (p = 0.01) 以及 Ki-67 (p = 0.017) 的表达相关。相比之下，细胞质 UP-STAT 与 Bcl-xl mRNA (p = 0.024) 和蛋白质 (p = 0.001) 以及细胞质生存素蛋白表达 (p = 0.019) 显着相关。结论：非活性 (UP-STAT3) 和活性 (P-STAT3) STAT3 蛋白在侵袭性 CRC 中均显着增加。这与 Bcl-xl 和生存素诱导、增殖增加和淋巴结转移有关。因此，本研究为进一步检查这些分子标志物在结直肠癌中的预后或预测价值提供了基础。
Aims: To evaluate mRNA and protein expression of signal transducers and activators of transcription (STAT) 3 in colorectal carcinomas (CRCs) and to define the association of STAT3 activity with the STAT3-inducible targets cyclin D1, survivin, Bcl-xl and Mcl-1.Materials and methods: Matching serial sections of normal colonic epithelium and invasive CRCs (n = 32) were subjected to quantitative reverse transcriptase polymerase chain reaction specific to STAT3, cyclin D1, survivin, Bcl-xl and Mcl-1, as well as immunohistochemistry. For STAT3 immunohistochemistry, two antibodies, recognising unphosphorylated (UP-) and phosphorylated (tyr705, P-) STAT3 were used. Ki-67 (MIB-1) staining was included as a proliferation marker.Results: Compared with normal colonic epithelium, UP-STAT3 and P-STAT3 (p = 0.023 and 0.006) protein expression and expression of its associated targets cyclin D1, survivin and Bcl-xl were significantly (all p < 0.001) increased in carcinoma. In carcinomas, STAT3 (p = 0.019) and Bcl-xl (p = 0.001) mRNAs were correlated with lymph node status. Moreover, nuclear P-STAT3 protein expression (active state) was associated with the expression of its target genes Bcl-xl (p = 0.038) and survivin (p = 0.01) as well as with Ki-67 (p = 0.017). By contrast, cytoplasmic UP- STAT was significantly linked to Bcl-xl mRNA (p = 0.024) and protein (p = 0.001) as well as to cytoplasmic survivin protein expression (p = 0.019).Conclusion: Both inactive (UP- STAT3) and active (P-STAT3) STAT3 proteins are markedly increased in invasive CRCs. This is associated with Bcl-xl and survivin induction, increased proliferation and lymph node metastasis. This study therefore provides the basis for further examination of the prognostic or predictive value of these molecular markers in CRC.