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Perspectives
Is the Loss of pRb Essential for the Mouse Skin
Sergio Ruiz, Mirentxu Santos and Jesús M. Paramio
volume 5 | issue 6
16 march 2006Pages: 625 - 630
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The pRb pathway is inactivated in most, if not all, human and mouse tumors, including skin tumors. However, a relatively low frequency of Rb gene alterations is found. The embryonic lethality of pRbdeficient animals restricts the analysis of these mice to midgestation and precludes the analysis of the roles of pRb in mouse cancer models. To solve this problem, we used the Cre/LoxP technology to induce the tissue-specific deletion of pRb. In epidermis, pRb deletion leads to altered proliferation and differentiation but these alterations do not induce the development of spontaneous skin tumors. To gain insight in the possible roles of pRb in mouse skin carcinogenesis, we have performed chemical tumorigenesis experiments in mice bearing epidermal-specific inactivation of Rb gene. Unexpectedly, these mice develop fewer and smaller tumors than control animals, but showing increased malignant conversion to squamous cell carcinomas. Detailed biochemical analysis demonstrates that, in the absence of pRb, multiple pathways are activated leading to increased tumor apoptosis. In particular, we characterized the aberrant p53 activation mediated by E2F/p19ARF and other transduction pathways. This may generate a selective pressure in the tumor leading to premature p53 loss of function, which ultimately results in increased malignancy. Overall, these data highlights the role of pRb during the malignant conversion in the mouse skin carcinogenesis, and the intimate relationships between pRb and multiple tumor suppressor networks in this system.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.