TY - JOUR
T1 - MMTV promoter-regulated caveolin-1 overexpression yields defective parenchymal epithelia in multiple exocrine organs of transgenic mice
AU - Yang, G.
AU - Park, S.
AU - Cao, G.
AU - Goltsov, A.
AU - Ren, C.
AU - Truong, L. D.
AU - DeMayo, F.
AU - Thompson, T. C.
PY - 2010/8
Y1 - 2010/8
N2 - 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.
AB - 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.
KW - Cav-1 overexpression
KW - Exocrine organs
KW - MMTV promoter
KW - Parenchymal epithelia
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U2 - 10.1016/j.yexmp.2010.03.009
DO - 10.1016/j.yexmp.2010.03.009
M3 - Article
C2 - 20399205
AN - SCOPUS:77954035774
VL - 89
SP - 9
EP - 19
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
SN - 0014-4800
IS - 1
ER -