Kallassy M, Toftgård R, Ueda M, Nakazawa K, Vorechovský I, Yamasaki H, Nakazawa H
Unit of Multistage Carcinogenesis, IARC, WHO, Lyon, France.
Cancer Res. 1997 Nov 1;57(21):4731-5.
The discovery of specific overexpression of a gatekeeper gene, ptch, in basal cell carcinoma (BCC) led to a hypothesis that the human homologue of patched (PTCH) normally functions as a negative regulator of the signaling pathway that is initiated by hedgehogs (HHs) and activated by the human homologue of smoothened (SMOH); however, no evidence for the involvement of smoh and hhs has been provided. Here, we show novel evidence that smoh is also preferentially overexpressed in BCC, together with ptch (P < 0.002), and that Sonic hh was expressed in only some BCCs. Our data, therefore, indicate that such overexpression of smoh may be associated with overexpression or mutation of PTCH and that this overexpression subsequently stimulates the PTCH/SMOH signaling pathway. In an investigation of a possible regulation of ptch and smoh, we demonstrated that expression of exogenous p21WAF1 in immortalized keratinocytes down-regulates both ptch and smoh and that the down-regulation is accompanied by growth arrest, which suggests the involvement of p21WAF1 in regulation of the PTCH/SMOH signaling pathway.
在基底细胞癌（BCC）中发现一种“守门”基因ptch的特异性过表达，这引发了一种假说，即patched（PTCH）的人类同源物通常作为由刺猬蛋白（HHs）启动并由smoothened（SMOH）的人类同源物激活的信号通路的负调节因子；然而，尚未有证据表明smoh和HHs参与其中。在此，我们展示了新的证据，即smoh也与ptch一起在BCC中优先过表达（P < 0.002），并且只有部分BCC中表达了Sonic hh。因此，我们的数据表明，smoh的这种过表达可能与PTCH的过表达或突变相关，并且这种过表达随后会刺激PTCH/SMOH信号通路。在对ptch和smoh可能的调控进行研究时，我们证明在永生化角质形成细胞中外源p21WAF1的表达会下调ptch和smoh，并且这种下调伴随着生长停滞，这表明p21WAF1参与了PTCH/SMOH信号通路的调控。
