Immortalization of pituitary cells at discrete stages of development by directed oncogenesis in transgenic mice
| Autor: | Elaine T. Alarid, Pamela L. Mellon, David B. Whyte, Jolene J. Windle |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Male
Carcinogenicity Tests Transgene Antigens Polyomavirus Transforming LIM-Homeodomain Proteins Gene Expression Mice Transgenic Biology medicine.disease_cause Gonadotropic cell Gonadotropin-Releasing Hormone Mice Pituitary Hormones Anterior medicine Tumor Cells Cultured Animals Humans Pituitary Neoplasms Progenitor cell Receptor Molecular Biology Transcription factor Homeodomain Proteins Mice Inbred BALB C Mice Inbred ICR Cell Differentiation Oncogenes Molecular biology Cell biology Mice Inbred C57BL Cell culture Pituitary Gland Female Carcinogenesis Immortalised cell line Developmental Biology Transcription Factors |
| Zdroj: | Development (Cambridge, England). 122(10) |
| ISSN: | 0950-1991 |
| Popis: | Targeted expression of oncogenes in transgenic mice can immortalize specific cell types to serve as valuable cultured model systems. Utilizing promoter regions from a set of genes expressed at specific stages of differentiation in a given cell lineage, we demonstrate that targeted oncogenesis can produce cell lines representing sequential stages of development, in essence allowing both spatial and temporal immortalization. Our strategy was based on our production of a committed but immature pituitary gonadotrope cell line by directing expression of the oncogene SV40 T antigen using a gonadotrope-specific region of the human glycoprotein hormone α-subunit gene in transgenic mice. These cells synthesize α-subunit and gonadotropinreleasing hormone (GnRH) receptor, yet are not fully differentiated in that they do not synthesize the β-subunits of luteinizing hormone (LH) or follicle-stimulating hormone (FSH). This observation lead to the hypothesis that targeting oncogenesis with promoters that are activated earlier or later in development might immortalize cells that were more primitive or more differentiated, respectively. To test this hypothesis, we used an LHβ promoter to immortalize a cell that represents a subsequent stage of gonadotrope differentiation (expression of α-subunit, GnRH receptor, and LH β-subunit but not FSH β-subunit). Conversely, targeting oncogenesis with a longer fragment of the human α-subunit gene (which is activated earlier in development) resulted in the immortalization of a progenitor cell that is more primitive, expressing only the α-subunit gene. Interestingly, this transgene also immortalized cells of the thyrotrope lineage that express both α- and β-subunits of thyroid-stimulating hormone and the transcription factor GHF-1 (Pit-1). Thus, targeted tumorigenesis immortalizes mammalian cells at specific stages of differentiation and allows the production of a series of cultured cell lines representing sequential stages of differentiation in a given cell lineage. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|