An in vitro model of the early genetic events in multistage carcinogenesis of malignant insulinoma

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Abstract

The aim of this study was to establish an in vitro model to confirm earlier observations on the role of the myc/ras oncogenes as promoting factors in the process of normal Langerhans islet β cell transformation. For that purpose we infected primary mouse Langerhans islets with a recombinant retrovirus containing the v-H-ras and v-myc oncogenes, before or after treatment with transforming growth factor α (TGFα). Normal Langerhans islets, when grown in culture, are viable for 2-3 weeks. After treatment with TGFα, viability was extended by 10 days, following which islets disintegrated. Langerhans islets transformed with v-H-ras and v-myc became immortal and insulin negative. Single infected β cells, liberated from a primary islet into the surrounding medium, gave rise to neo islet formation. Moreover, single infected β cells were able to grow and divide, even without fibroblast support. These results indicate that the myc and ras oncogenes are sufficient for commencement of β cell transformation and, therefore, could represent 'early events' in the multistep carcinogenesis of insulinomas.

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Katić, M., Hadžija, M., Wrischer, M., & Pavelić, K. (1999). An in vitro model of the early genetic events in multistage carcinogenesis of malignant insulinoma. Carcinogenesis, 20(8), 1521–1527. https://doi.org/10.1093/carcin/20.8.1521

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