Multiple endocrine neoplasia induced by the promiscuous expression of a viral oncogene

R. K. Reynolds, G. S. Hoekzema, J. Vogel, S. H. Hinrichs, G. Jay

Research output: Contribution to journalArticle

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Abstract

There is increasing evidence for the importance of events that govern and influence the interaction between the transformed cell and its host being ultimately responsible for the establishment of the cancer phenotype. To derive an animal model that will allow us to define some of these phenomena at the molecular level, we have chosen to induce the expression of a viral oncogene in all tissue types, with the hope of identifying sites that are more susceptible to malignant transformation. When the gene for simian virus 40 large tumor antigen (T antigen) was placed under the control of a major histocompatibility complex class I gene enhancer, the resulting transgenic mice not only developed choroid plexus papillomas, as seen with wild-type simian virus 40, but also lymphoid hyperplasia and multiple endocrine neoplasias. The development of lymphoid hyperplasia was preceded by an elevated level of expression of T antigen in these tissues at an early age. Surprisingly, the striking thymic hyperplasia has not been observed to progress toward malignancy. The multiple endocrine neoplasias developed later in life and involved the pancreas, pituitary, thyroid, adrenals, and testes. While not preceded by an elevated level of expression of T antigen, once endocrine tumors appeared they quickly progressed toward malignant growth. Although other tissues also exhibited a basal level of expression of the viral oncogene similar to that detected in endocrine tissues, they rarely developed tumors. This transgenic mouse model seems particularly suitable for a molecular understanding of events responsible for certain tissue types being so much more susceptible to neoplastic conversion, with others being so refractory.

Original languageEnglish (US)
Pages (from-to)3135-3139
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number9
DOIs
StatePublished - Jan 1 1988

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Multiple Endocrine Neoplasia
Oncogenes
Neoplasm Antigens
Simian virus 40
Transgenic Mice
Hyperplasia
Neoplasms
Thymus Hyperplasia
Choroid Plexus Papilloma
MHC Class I Genes
Major Histocompatibility Complex
Testis
Pancreas
Thyroid Gland
Animal Models
Phenotype
Growth
Genes

ASJC Scopus subject areas

  • General

Cite this

Multiple endocrine neoplasia induced by the promiscuous expression of a viral oncogene. / Reynolds, R. K.; Hoekzema, G. S.; Vogel, J.; Hinrichs, S. H.; Jay, G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 85, No. 9, 01.01.1988, p. 3135-3139.

Research output: Contribution to journalArticle

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