MMTV promoter-regulated caveolin-1 overexpression yields defective parenchymal epithelia in multiple exocrine organs of transgenic mice.
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.
Yang
Guang
G
Department of Genitourinary Medical Oncology-Research, Unit 18-3, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA. guangyang@mdanderson.org
Park
Sanghee
S
Cao
Guangwen
G
Goltsov
Alexei
A
Ren
Chengzhen
C
Truong
Luan D
LD
Demayo
Francesco
F
Thompson
Timothy C
TC
D000015:Abnormalities, Multiple / Q000235:genetics*; D000818:Animals; D051242:Caveolin 1 / Q000235:genetics*; D002478:Cells, Cultured; D004848:Epithelium / Q000378:metabolism / Q000473:pathology*; D005088:Exocrine Glands / Q000002:abnormalities*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006965:Hyperplasia; D015994:Incidence; D008113:Liver Neoplasms / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D008321:Mammary Glands, Animal / Q000002:abnormalities; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012867:Skin / Q000378:metabolism / Q000473:pathology
D051242:Caveolin 1
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