Expression of a dominant negative type II TGF-β receptor in mouse skin results in an increase in carcinoma incidence and an acceleration of carcinoma development
Expression of a dominant negative type II TGF-β receptor in mouse skin results in an increase in carcinoma incidence and an acceleration of carcinoma development
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DOI：
10.1038/sj.onc.1202161
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发表时间：
1998-07-09
期刊：
影响因子：
8
通讯作者：
Blessing, M
中科院分区：
文献类型：
--
作者：
Amendt, C;Schirmacher, P;Blessing, M
The role of Transforming growth factor beta (TGF-beta) in carcinogenesis is complex. There are reports on both tumor inhibition and tumor promotion by TGF-beta. To elucidate the complex role of TGF-beta in epithelial carcinogenesis, we generated transgenic mice overexpressing a dominant negative type II TGF-beta receptor in the basal cell compartment and in follicular cells of the skin, Despite the reduced responsiveness of transgenic keratinocytes to TGF-beta, both proliferation and differentiation were normal in non-irritated epidermis of these transgenic mice, Thus, interruption of signaling of all three isoforms of TGF-beta in basal and follicular cells does not disturb tissue homeostasis. However, during tumor promotion transgenic mice showed an elevated level of proliferation in the epidermis. This hyperproliferation correlated with a very early onset of carcinoma development and a malignant conversion frequency of 30% from benign papillomas to carcinomas. By comparison, the conversion frequency in wild-type mice of this strain has previously been reported as 5.5%, Even without induction of hyperproliferation by tumor promoters, transgenic mice developed far more carcinomas as controls when treated with a carcinogen. This result indicates that there is a synergistic effect between loss of TGF-beta responsiveness and mutations caused by initiation with a carcinogen leading to an endogeneous tumor promotion in initiated cells only.
