Talamonti M S, Roh M S, Curley S A, Gallick G E
Department of Surgery, University of Texas M.D. Anderson Cancer Center, Houston 77030.
J Clin Invest. 1993 Jan;91(1):53-60. doi: 10.1172/JCI116200.
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.
已证明，在几乎每一例原发性结直肠癌中都会出现c-src基因产物pp60c-src的酪氨酸激酶激活，并且早在具有高恶性潜能的息肉中就已发现。然而，尚无研究探讨进展过程中可能发生的pp60c-src变化。为了研究这个问题，我们研究了7个结肠息肉、19个原发性病变以及19个肝转移灶相对于正常结肠黏膜的激酶活性和蛋白水平。早在具有高恶性潜能的结肠息肉中就观察到酪氨酸激酶活性显著增加。在原发性肿瘤中，活性和水平进一步升高。然而，在肝转移灶中观察到活性和蛋白水平的最大幅度增加。此外，还获取了6个转移灶，其中同步切除了原发性肿瘤。在每一个这些肝转移灶中，相对于相应的原发性肿瘤以及正常结肠黏膜，pp60c-src活性和水平均显著增加。我们的结果表明，结肠原发性肿瘤向肝转移的进展与pp60c-src激酶活性和蛋白水平增加相关。
