Heterotopic endochondrial ossification with mixed tumor formation in C3(1)/Tag transgenic mice is associated with elevated TGF-beta1 and BMP-2 expression.

Heterotopic endochondrial ossification with mixed tumor formation in C3(1)/Tag transgenic mice is associated with elevated TGF-beta1 and BMP-2 expression. Research Abstract Details 

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Heterotopic endochondrial ossification with mixed tumor formation in C3(1)/Tag transgenic mice is associated with elevated TGF-beta1 and BMP-2 expression. Abstract Text:

I G Maroulakou,M A Shibata,M Anver,C L Jorcyk,M l Liu,N Roche,A B Roberts,I Tsarfaty,J Reseau,J Ward,J E Green,

Transgenic mice which express the simian virus 40 large T-antigen (Tag) under the regulatory control of the hormone responsive rat C3(1) gene develop unusual lesions of heterotopic bone growth associated with mixed tumor formation arising from eccrine sweat glands found only in the foot pads of mice, ischiocavernosus muscle adjacent to bulbourethral glands and occasionally the salivary and mammary glands. These lesions are very similar to mixed tumors arising in several types of human cancers. Based upon electron microscopic examination and immunocytochemical analyses of cellular differentiation markers, the mixed proliferative lesions in this transgenic mouse model begin with the Tag-induced proliferation of epithelial and myoepithelial cells. The proliferation of these two types of cells results in hyperplasia and adenomatous transformation of the epithelial component, whereas the proliferating myoepithelial cells undergo metaplasia to form chondrocytes which deposit extracellular matrix, including collagen fibers. Cartilage develops focally between areas of epithelial proliferation and subsequently ossifies through a process of endochondrial bone formation. The metaplasia of myoepithelial cells to chondrocytes appears to require the inductive interaction of factors produced by the closely associated proliferating epithelial cells, including members of the TGF-beta superfamily. We demonstrate that TGF-beta1 protein accumulates in the extracellular matrix of the lesions, whereas RNA in situ hybridization reveals that BMP-2, another strong inducer of heterotopic bone formation, is overexpressed by the proliferating epithelial cells during the development of ectopic bone. The formation of sarcomatous tumors within the mixed tumors appears to be androgen-dependent and more frequent in mice lacking a normal allele of p53. This process of cartilage and bone induction may mimic epithelial-mesenchymal interactions which occur during embryonic bone formation. These transgenic mice may provide new insights into the processes of ectopic endochondrial bone formation associated with mixed tumor formation and serve as a useful model for human heterotopic bone disease.

Heterotopic endochondrial ossification with mixed tumor formation in C3(1)/Tag transgenic mice is associated with elevated TGF-beta1 and BMP-2 expression. Publishing Authors By Initials

IG Maroulakou,MA Shibata,M Anver,CL Jorcyk,M Liu,N Roche,AB Roberts,I Tsarfaty,J Reseau,J Ward,JE Green,

For similar macromolecular substances: polymers: biopolymers: intermediate filament proteins: vimentin research abstracts see: macromolecular substances: polymers: biopolymers: intermediate filament proteins: vimentin research

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Heterotopic endochondrial ossification with mixed tumor formation in C3(1)/Tag transgenic mice is associated with elevated TGF-beta1 and BMP-2 expression. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Oncogene

VOLUME: 18

Page Numbers: 5435-47

Journal Abbreviation: Oncogene

ISSN: 0950-9232

DAY: 23

MONTH: Sep

YEAR: 1999

Heterotopic endochondrial ossification with mixed tumor formation in C3(1)/Tag transgenic mice is associated with elevated TGF-beta1 and BMP-2 expression. Information

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LANGUAGE: eng

NlmUniqueID: 8711562

Heterotopic endochondrial ossification with mixed tumor formation in C3(1)/Tag transgenic mice is associated with elevated TGF-beta1 and BMP-2 expression. Keywords Mesh Terms:

KEYWORDS: Vimentin

MESH TERMS: analysis

Chemical & Substance for Abstract: Heterotopic endochondrial ossification with mixed tumor formation in C3(1)/Tag transgenic mice is associated with elevated TGF-beta1 and BMP-2 expression. Information

Substance Name: Tolonium Chloride

Registry Number: 92-31-9

Grant and Affiliation Information for Heterotopic endochondrial ossification with mixed tumor formation in C3(1)/Tag transgenic mice is associated with elevated TGF-beta1 and BMP-2 expression.

AFFILIATION: Laboratory of Cell Regulation and Carcinogenesis, NCI, Bethesda, Maryland, MD 20892, USA.

Country: ENGLAND

AGENCY: United States NCI

GRANT: N01CO56000

ACRONYM: CO

MEDLINETA: Oncogene

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