MMTV promoter-regulated caveolin-1 overexpression yields defective parenchymal epithelia in multiple exocrine organs of transgenic mice

G. Yang, S. Park, G. Cao, A. Goltsov, C. Ren, L. D. Truong, F. DeMayo, T. C. Thompson

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Caveolin-1 (Cav-1) is a major structural protein of caveolae, specialized plasma membrane invaginations that are involved in a cell-specific fashion in diverse cell activities such as molecular transport, cell adhesion, and signal transduction. In normal adult mammals, Cav-1 expression is abundant in mesenchyme-derived cells but relatively low in epithelial parenchyma. However, epithelial Cav-1 overexpression is associated with development and/or progression of many carcinomas. In this study, we generated and characterized a transgenic mouse model of Cav-1 overexpression under the control of a mouse mammary tumor virus (MMTV) long terminal-repeat promoter, which is predominantly expressed in specific epithelial cells. The MMTVcav-1+ transgenic mice were fertile, and females bore litters of normal size with no obvious developmental abnormalities. However, by age 11months, the MMTVcav-1+ mice demonstrated overtly different phenotypes in multiple exocrine organs when compared with their nontransgenic MMTVcav-1- littermates. Cav-1 overexpression in MMTVcav-1+ mice produced organ-specific abnormalities, including hypotrophy of mammary glandular epithelia, bronchiolar epithelial hyperplasia and atypia, mucous-cell hyperplasia in salivary glands, elongated hair follicles and dermal thickening in the skin, and reduced accumulation of enzymogen granules in pancreatic acinar cells. In addition, the MMTVcav-1+ transgenic mice tended to have a greater incidence of malignant tumors, including lung and liver carcinomas and lymphoma, than their MMTVcav-1- littermates. Our results indicate that Cav-1 overexpression causes organ-specific, age-related epithelial disorders and suggest the potential for increased susceptibility to carcinogenesis.

Original languageEnglish (US)
Pages (from-to)9-19
Number of pages11
JournalExperimental and Molecular Pathology
Volume89
Issue number1
DOIs
StatePublished - Aug 2010

Keywords

  • Cav-1 overexpression
  • Exocrine organs
  • MMTV promoter
  • Parenchymal epithelia

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Pathology and Forensic Medicine

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