Calcitonin driven v-Ha-ras induces multilineage pulmonary epithelial hyperplasias and neoplasms.

Journal Article (Journal Article)

We initiated a transgenic model for primary pulmonary neuroendocrine cell (PNEC) hyperplasia/neoplasia using v-Ha-ras driven by the neural/neuroendocrine (NE)-specific calcitonin promoter (rascal). Previously, we showed that nitrosamine treated rodents develop PNEC hyperplasia but non-NE lung tumors, with variable outcomes presumably reflecting ras activation in multiple cell lineages. Interestingly, all rascal transgenic mouse lineages develop hyperplasias of NE and non-NE cells but mostly non-NE lung carcinomas, with rascal mRNA in differentiated PNECs and tumor cells. Analyses of embryonic lung demonstrate rascal mRNA in undifferentiated epithelium, consistent with expression in a common pluripotent precursor cell. These unexpected observations indicate that v-Ha-ras can lead to both NE and non-NE hyperplasia/neoplasia in vivo, opening new avenues for studies of lung carcinogenesis.

Full Text

Duke Authors

Cited Authors

  • Sunday, ME; Haley, KJ; Sikorski, K; Graham, SA; Emanuel, RL; Zhang, F; Mu, Q; Shahsafaei, A; Hatzis, D

Published Date

  • July 29, 1999

Published In

Volume / Issue

  • 18 / 30

Start / End Page

  • 4336 - 4347

PubMed ID

  • 10439041

International Standard Serial Number (ISSN)

  • 0950-9232

Digital Object Identifier (DOI)

  • 10.1038/sj.onc.1202810


  • eng

Conference Location

  • England