Journal Article

An <i>in vitro</i> model of the early genetic events in multistage carcinogenesis of malignant insulinoma

Maša Katić, Mirko Hadžija, Mercedes Wrischer and Krešimir Pavelić

in Carcinogenesis

Volume 20, issue 8, pages 1521-1528
Published in print August 1999 | ISSN: 0143-3334
Published online August 1999 | e-ISSN: 1460-2180 | DOI:
An in vitro model of the early genetic events in multistage carcinogenesis of malignant insulinoma

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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.

Keywords: c.f.u., colony forming units; EGF-R, epidermal growth factor receptor; FCS, fetal calf serum; HeBS, HEPES-buffered saline pH 7.05; PBS, phosphate-buffered saline; TGFα, transforming growth factor α

Journal Article.  4577 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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