Hyperplasia and impaired involution in the mammary gland of transgenic mice expressing human FGF4

Autor: Cristina Ricotta, Ottavia Barbieri, Mara Rossini, Nicoletta Ferrari, Monica Morini, Marirosa Mora, Stefano Mantero, Simonetta Astigiano, Giovanni Levi
Rok vydání: 2001
Předmět:
Vascular Endothelial Growth Factor A
Cancer Research
Aging
Angiogenesis
medicine.medical_treatment
Mammary gland
Apoptosis
Endothelial Growth Factors
Fibroblast growth factor
Malignant transformation
Mice
Pregnancy
Transgenes
Promoter Regions
Genetic
Lymphokines
Neovascularization
Pathologic
Vascular Endothelial Growth Factors
Milk Proteins
Immunohistochemistry
medicine.anatomical_structure
Cell Transformation
Neoplastic
Phenotype
Female
Whey Acidic Protein
medicine.medical_specialty
Blotting
Western
Fibroblast Growth Factor 4
Mammary Neoplasms
Animal
Mice
Transgenic
Biology
Mammary Glands
Animal
Internal medicine
Proto-Oncogene Proteins
FGF4
Genetics
medicine
Animals
Humans
Lactation
Involution (medicine)
RNA
Messenger
Molecular Biology
Hyperplasia
Growth factor
Epithelial Cells
Fibroblast Growth Factors
Endocrinology
Gene Expression Regulation
Cancer research
biology.protein
Zdroj: Oncogene. 19(52)
ISSN: 0950-9232
Popis: Fgf4, a member of the fibroblast growth factor family, is frequently amplified in a variety of human cancers, however, its expression in neoplastic tissues is rarely detectable. This makes uncertain its involvement in tumour aetiology, although several in-vitro studies link Fgf4 overexpression to malignant transformation and metastatization of culture cells. We generated a transgenic mouse model in which the whey acidic protein (WAP) promoter directs expression of human Fgf4 to mammary tissues during late pregnancy and throughout lactation, with the purpose of studying the involvement of this growth factor in mammary tumorigenesis. Expression of the transgene was specifically detected in lobular-alveolar cells of lactating mammary glands that, by histological analysis, displayed hyperplastic areas and a disorganized structure. This was accompanied by an increased number of red blood cells and expression, in alveolar epithelial cells, of the vascular endothelial growth factor, which is absent in wild type controls. The most striking effect caused by FGF4 overexpression was on the remodelling of mammary tissue at the end of lactation. Indeed, transgenic animals showed a delayed involution of the gland due to a dramatic reduction in the overall number of apoptotic cells, which are normally present in the organ after weaning. Nevertheless, none of the animals examined developed neoplastic lesions of the mammary gland even after several pregnancies and at old age. Our work represents the first in-vivo demonstration of the anti-apoptotic and angiogenic properties of FGF4.
Databáze: OpenAIRE
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