Id2 Is Dispensable for Myc-Induced Epidermal Neoplasia

Abstract

We have previously described a transgenic mouse model of epidermal neoplasia wherein expression of a switchable form of c-Myc, MycER^TAM, is targeted to the postmitotic suprabasal keratinocytes of murine epidermis via the involucrin promoter. Sustained activation of c-MycER^TAM results in a progressive neoplastic phenotype characterized by aberrant ectopic proliferation and delayed differentiation of suprabasal keratinocytes, culminating in papillomatosis. Transcription of the Id2 gene is regulated by Myc family proteins. Moreover, Id2 is implicated as a pivotal determinant of cell fate in multiple lineages and has a demonstrated role in mediating Myc-dependent cell proliferation in vitro through its interaction with retinoblastoma protein. Using Id2 nullizygous mice, we assessed in vivo the requirement for Id2 in mediating Myc-induced papilloma formation in skin. We show that absence of Id2 has no discernible impact on any measurable attribute of Myc function or on the timing or extent of eventual tumor formation. Thus, our data argue against any essential role for Id2 in mediating Myc action in vivo.

This work was supported by grants from Mt. Zion Health Systems, Inc., San Francisco, Calif., and National Institutes of Health grant 5P30 CA23108-24. D.J.M. is supported by National Research Service award 1 F32 CA99363-01 from the National Cancer Institute.

We thank Tobias Dansen, David Elson, Ignacio Flores, and Jin-Sea Rhee for technical assistance and Luika Timmerman for critical evaluation of the manuscript.