Identification and evaluation of the role of endogenous tyrosine kinases in azoxymethane induction of proliferative processes in the colonic mucosa of rats.
Identification and evaluation of the role of endogenous tyrosine kinases in azoxymethane induction of proliferative processes in the colonic mucosa of rats.
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鉴定和评估内源性酪氨酸激酶在氧化偶氮甲烷诱导大鼠结肠粘膜增殖过程中的作用。
DOI：
10.1016/0304-4165(95)00024-6
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Majumdar,AP
中科院分区：
文献类型：
--
作者：
Relan,NK;Saeed,A;Ponduri,K;Fligiel,SE;Dutta,S;Majumdar,AP
虽然酪氨酸激酶（Tyr-k）已知在调节正常细胞、癌前细胞和肿瘤细胞的增殖中起作用，但对参与该过程的不同种类的Tyr-k的身份知之甚少。利用非变性聚丙烯酰胺凝胶电泳系统，其中从组织提取物中分离的蛋白质直接测定Tyr-k，我们试图确定可能参与氧化偶氮甲烷（AOM）诱导结肠粘膜鸟氨酸脱羧酶（ODC）活性的Tyr-k的种类，该酶的活性已知在快速增殖的细胞中升高。我们观察到，在单次注射结肠致癌物AOM（20 mg/kg体重）后5天，3-4月龄大鼠结肠粘膜增殖活性显著增加230%（5-溴-2 ′-脱氧尿苷（BrdU）免疫反应性证实），同时ODC活性增加550%。这还与Mrof为165、145和125 kDa的三种粘膜蛋白的Tyr-k相对活性显着升高（140-240%）有关。由于Tyr-k之一（165 kDa）的分子量对应于EGF受体（EGF-R）的分子量，因此我们研究了EGF-R Tyr-k在AOM诱导结肠粘膜ODC中的作用。我们观察到，AOM注射后5天，粘膜ODC活性增加320%，同时EGF-R的Tyr-k活性增加超过200%。每日注射酪氨酸磷酸化抑制剂（300 μg/kg体重），一种对EGF-R Tyr-k具有更高特异性的Tyr-k抑制剂，显著减弱AOM诱导的ODC和EGF-R Tyr-k活性的刺激。AOM还可刺激结肠细胞合成和分泌TGF-α。此外，AOM组大鼠结肠粘膜TGF-α及其mRNA水平分别比对照组高100%和250%。我们认为（a）EGF-R的内在Tyr-k的激活是AOM诱导结肠粘膜增殖过程中的重要事件，（B）这种激活被认为是由TGF-α通过自分泌机制介导的。
Although tyrosine kinases (Tyr-k) are known to play a role in regulating proliferation of normal, preneoplastic and neoplastic cells, little is known about the identity of different species of Tyr-k involved in this process. Utilizing a non-denaturing polyacrylamide gel electrophoresis system, in which the separated proteins from tissue extracts are assayed directly for Tyr-k, we attempted to identify the species of Tyr-k that may be involved in azoxymethane (AOM) induction of colonic mucosal ornithine decar☐ylase (ODC) activity, an enzyme whose activity is known to rise in rapidly proliferating cells. We have observed that 5 days after a single injection of the colonic carcinogen AOM (20 mg/kg body wt.) to 3–4-month old rats, a significant 230% rise in colonic mucosal proliferative activity (as evidenced by 5-bromo-2′-deoxyuridine (BrdU) immunoreactivity) was also accompanied by a 550% increase in ODC activity. This was also associated with a marked rise (140–240%) in the relative activity of Tyr-k of three mucosal proteins with Mrof 165, 145 and 125 kDa. Since the molecular mass of one of the Tyr-k (165 kDa) corresponded to that of EGF-receptor (EGF-R), this led us to examine the role of EGF-R Tyr-k in AOM induction of colonic mucosal ODC. We observed that a 320% increase in mucosal ODC activity, 5 days after AOM injection, was accompanied by over 200% rise in Tyr-k activity of EGF-R. Daily injection of tyrphostin (300 μg/kg body wt.), a Tyr-k inhibitor with a higher specificity for EGF-R Tyr-k, significantly attenuated AOM-induced stimulation of both ODC and Tyr-k activity of EGF-R. Administration of AOM also stimulated the rate of synthesis and secretion of TGF-α in isolated colonocytes. In addition, the levels of TGF-α and its mRNA in the colonic mucosa were also found to be 100% and 250% higher, respectively, in AOM-treated rats when compared with the controls. We suggest that (a) activation of intrinsic Tyr-k of EGF-R is an important event in AOM induction of colonic mucosal proliferative processes, and (b) this activation is thought to be mediated by TGF-α through an autocrine mechanism.
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DOI：
10.1111/j.1349-7006.1990.tb02505.x
发表时间：
1990-01
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Yoshida K;Kyo E;Tsujino T;Sano T;Niimoto M;Tahara E
通讯作者：
Tahara E
使用非变性聚丙烯酰胺凝胶电泳分析细胞提取物中的酪氨酸激酶活性。
影响因子：
2.9
作者：
R. I. Glazer;G. Yu;M. C. Knode
通讯作者：
M. C. Knode
大鼠衰老过程中胃粘膜酪氨酸激酶活性及其与细胞增殖的关系。
DOI：
10.1016/0304-4165(88)90043-8
发表时间：
1988
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Adhip P. Nandi Manjmdar;Adhip P. Nandi Manjmdar;Elizabeth A. Edgerton
通讯作者：
Elizabeth A. Edgerton
增生性息肉和腺瘤性息肉患者直肠粘膜中鸟氨酸脱羧酶和酪氨酸激酶的差异激活。
影响因子：
29.4
作者：
J. Colarian;F. Arlow;R. Calzada;G. Luk;A. P. Majumdar
通讯作者：
A. P. Majumdar
正常人胃肠道粘膜中转化生长因子α和表皮生长因子水平。
影响因子：
8.8
作者：
Cartlidge, S A;Elder, J B
通讯作者：
Elder, J B