Stabilization of β-catenin induces lesions reminiscent of prostatic intraepithelial neoplasia, but terminal squamous transdifferentiation of other secretory epithelia

Fotini Gounari, Sabina Signoretti, Roderick Bronson, Ludger Klein, William R. Sellers, Jennifer Kum, Anja Siermann, Makoto M. Taketo, Harald Von Boehmer, Khashayarsha Khazaie

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

The present study documents that stabilization of β-catenin is sufficient to induce lesions reminiscent of prostate intraepithelial neoplasia (PIN). Such lesions were present in all compound mutant mice and all prostate acini expressing stabilized β-catenin. High grade PIN-like lesions resembling early human prostate cancer were detected as early as 10 weeks of age. Surprisingly, stabilization of β-catenin in other secretory epithelia including salivary, preputial, harderian, and mammary glands induced extensive squamous metaplasia and keratinization associated with terminal differentiation of the target cells, but failed to cause neoplastic transformation. Epidermal hyperplasia, hair follicle cysts, and odontomas were also observed. The prostatic lesions exhibited upregulation of c-myc, increased rate of cellular proliferation, loss of the Na-K-Cl co-transporter NKCC1, and expression of androgen receptor. Basal cell markers such as p63 and keratin 5 were not expressed by the masses of PIN-like lesions, but were present in small foci of proliferating β-catenin expressing basal cells. Our observations indicate that β-catenin stabilization is a crucial event for the initiation of PIN-like lesions, but induces squamous metaplasia rather than tumorigenesis in secretory epithelia other than the prostate.

Original languageEnglish (US)
Pages (from-to)4099-4107
Number of pages9
JournalOncogene
Volume21
Issue number26
DOIs
StatePublished - Jan 1 2002

Keywords

  • Metaplasia
  • Neoplasia
  • Prostate
  • β-catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Gounari, F., Signoretti, S., Bronson, R., Klein, L., Sellers, W. R., Kum, J., Siermann, A., Taketo, M. M., Von Boehmer, H., & Khazaie, K. (2002). Stabilization of β-catenin induces lesions reminiscent of prostatic intraepithelial neoplasia, but terminal squamous transdifferentiation of other secretory epithelia. Oncogene, 21(26), 4099-4107. https://doi.org/10.1038/sj.onc.1205562