Abstract
Study of the molecular and cellular biology of the gonadotropin hormones would be greatly facilitated by the availability of immortalized anterior pituitary gonadotrope cell lines. We directed expression of the simian virus-40 (SV40) T-antigen (Tag) oncogene to specific cells in the anterior pituitary of transgenic mice using the promoter/enhancer region from the human glycoprotein hormone alpha-subunit gene. Transgenic mice carrying this fusion gene developed anterior pituitary tumors. Clonal cell lines established from these tumors express the endogenous mouse alpha-subunit gene and synthesize and secrete alpha-subunit protein. However, they do not express beta-subunit genes. Alpha-subunit mRNA is induced by GnRH in a dose- and time-dependent manner, but is not regulated by TRH. Thus, we have targeted tumorigenesis in transgenic mice to anterior pituitary cells of the gonadotrope lineage to immortalize this specific endocrine cell while maintaining several highly differentiated functions unique to gonadotropes.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, Polyomavirus Transforming / biosynthesis
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Antigens, Polyomavirus Transforming / genetics
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Antigens, Polyomavirus Transforming / toxicity*
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Cell Differentiation
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Cell Line*
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Gene Expression Regulation, Neoplastic / drug effects
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Genetic Vectors
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Glycoprotein Hormones, alpha Subunit / biosynthesis
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Glycoprotein Hormones, alpha Subunit / genetics*
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Glycoprotein Hormones, alpha Subunit / metabolism
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Gonadotropin-Releasing Hormone / pharmacology
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Mice
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Mice, Transgenic
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Oncogenes*
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Pituitary Gland, Anterior / pathology*
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Pituitary Hormones, Anterior / biosynthesis
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Pituitary Neoplasms / etiology
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Pituitary Neoplasms / pathology*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Recombinant Fusion Proteins / toxicity*
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Simian virus 40 / genetics
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Thyrotropin-Releasing Hormone / pharmacology
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Tumor Cells, Cultured / metabolism
Substances
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Antigens, Polyomavirus Transforming
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Glycoprotein Hormones, alpha Subunit
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Pituitary Hormones, Anterior
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Recombinant Fusion Proteins
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Gonadotropin-Releasing Hormone
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Thyrotropin-Releasing Hormone