Src kinase and mitogen-activated protein kinases in the progression from normal to malignant endometrium
Src kinase and mitogen-activated protein kinases in the progression from normal to malignant endometrium
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DOI：
10.1158/1078-0432.ccr-0661-03
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发表时间：
2004-01-15
影响因子：
11.5
通讯作者：
Rowan, BG
中科院分区：
文献类型：
--
作者：
Desouki, MM;Rowan, BG
目的：本研究的目的是确定激活的丝裂原活化蛋白激酶(MAPK)和Src激酶的水平与子宫内膜从正常到恶性进展之间是否存在相关性。实验设计：我们通过使用抗这些蛋白的抗体对33例冷冻子宫内膜腺癌和38例良性子宫内膜标本的蛋白质印迹信号进行定量，检测了细胞外信号调节激酶1/2、p38、应力激活蛋白激酶/c-jun NH2末端激酶和Src激酶的总水平和磷酸化水平。在良性和恶性子宫内膜中检测到磷酸化p38和磷酸化p38(分别为28+/-5和27+/-7，P<0.001)。癌组织中c-jun氨基末端激酶活性略高于良性组织(513vs43+/-10；P=0.8)。细胞外信号调节激酶1/2，9+/-2比0.7+/-0.1；Src，7+/-2比0.4+/-0.1；应激激活蛋白激酶c-jun NH2末端激酶，2+/-0.4比0.2+/-0.2；P<；0.001；p38，1+/-0.2比0.4+/-0.1；P<；0.01)。结论：与乳腺癌相比，子宫内膜癌从正常到恶性的发展与MAPK和MAPKs的活化无关。良性子宫内膜中这些活性激酶的升高可能有助于子宫内膜对他莫昔芬的抗雌激素作用的抵抗。
Purpose: The purpose of this research was to determine whether a correlation exists between the levels of activated mitogen-activated protein kinase (MAPK) and Src kinases and the progression from normal to malignant endometrium.Experimental Design: We measured total and phosphorylated levels for extracellular signal-regulated kinase 1/2, p38, stress- activated protein kinase/c-Jun NH2-terminal kinase, and Src kinases from 33 frozen endometrial adenocarcinomas and 38 benign endometrial specimens by quantitation of signals from Western blots using antibodies against these kinases.Results: Elevated phospho-extracellular signal-regulated kinase 1/2 (150 +/- 40 versus 46 +/- 7; P = 0.03), phospho-Src (28 +/- 5 versus 4 +/- 1), and phospho-p38 (131 +/- 16 versus 27 +/- 7; P < 0.001) was detected in benign versus malignant endometrium when the Western blot signal of activated kinase was normalized to total kinase levels and 0 actin. A modest increase in active c-Jun NH2-terminal kinase was detected in carcinoma versus benign specimens (51 13 versus 43 +/- 10; P = 0.8). Expression of total kinases (normalized to beta-actin) was higher in carcinoma versus benign specimens, respectively (extracellular signal-regulated kinase 1/2, 9 +/- 2 versus 0.7 +/- 0.1; Src, 7 +/- 2 versus 0.4 +/- 0.1; stress-activated protein kinase c-Jun NH2-terminal kinase, 2 +/- 0.4 versus 0.2 +/- 0.02; P < 0.001; and p38, 1 +/- 0.2 versus 0.4 +/- 0.1; P < 0.01). Immunohistochemistry for active and total Src kinases and MAPKs detected positive staining in epithelial and stroma cells.Conclusions: These data demonstrated that, in contrast with breast cancer, the progression from normal to malignant endometrium is not associated with activation of MAPK and Src kinases. Elevation of these active kinases in benign endometrium may contribute to endometrial resistance to the antiestrogen action of tamoxifen.