INCREASE IN ACTIVITY AND LEVEL OF PP60C-SRC IN PROGRESSIVE STAGES OF HUMAN COLORECTAL-CANCER
INCREASE IN ACTIVITY AND LEVEL OF PP60C-SRC IN PROGRESSIVE STAGES OF HUMAN COLORECTAL-CANCER
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DOI：
10.1172/jci116200
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发表时间：
1993-01-01
影响因子：
15.9
通讯作者：
GALLICK, GE
中科院分区：
文献类型：
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作者：
TALAMONTI, MS;ROH, MS;GALLICK, GE
c-src基因产物pp 60 c-src的酪氨酸激酶的激活已被证明发生在几乎每一种原发性结直肠癌中，并且早在高恶性潜能的息肉中被发现。然而，没有研究涉及在进展期间发生的潜在pp 60 c-src变化。为了验证这个问题，我们研究了7例结肠息肉、19例原发性病变和19例肝转移瘤中相对于正常结肠粘膜的激酶活性和蛋白水平。酪氨酸激酶活性的显着增加，早在结肠息肉的高恶性潜力。在原发性肿瘤中观察到活性和水平的进一步增加。然而，在肝转移中观察到活性和蛋白水平的最大增加。此外，获得6个转移病灶，其中同步原发肿瘤被切除。在这些肝转移瘤中的每一个中，pp 60 c-src活性和水平相对于相应的原发肿瘤以及正常结肠粘膜显著增加。我们的研究结果表明，结肠原发性肿瘤肝转移的进展与pp 60 c-src激酶活性和蛋白水平的增加相关。
Activation of the tyrosine kinase of the c-src gene product, pp60c-src, has been shown to occur in nearly every primary colorectal carcinoma, and is found as early as in polyps of high malignant potential. However, no studies have addressed potential pp60c-src changes which occur during progression. To examine this question, we have studied kinase activity and protein levels in 7 colonic polyps, 19 primary lesions, and 19 liver metastases relative to normal colonic mucosa. Significant increases in tyrosine kinase activity were seen as early as in colonic polyps of high malignant potential. Further increases were observed in activity and level in primary tumors. However, the greatest increases in activity and protein levels were observed in liver metastases. Additionally, six metastatic lesions were obtained in which synchronous primary tumor was resected. In each of these liver metastases, pp60c-src activity and level were significantly increased relative to the corresponding primary tumor, as well as to normal colonic mucosa. Our results demonstrate that progression of colon primary tumors to liver metastases correlates with increased pp60c-src kinase activity and protein level.