Multiple endocrine neoplasia induced by the promiscuous expression of a viral oncogene.
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.
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis / Q000235:genetics*; D002678:Chimera; D004247:DNA / Q000032:analysis; D004262:DNA Restriction Enzymes / Q000378:metabolism; D019003:Deoxyribonuclease HpaII; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009377:Multiple Endocrine Neoplasia / Q000235:genetics*; D009857:Oncogenes; D010641:Phenotype
D000952:Antigens, Polyomavirus Transforming; D004247:DNA; D004262:DNA Restriction Enzymes; D019003:Deoxyribonuclease HpaII