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.
- Sunday, ME; Haley, KJ; Sikorski, K; Graham, SA; Emanuel, RL; Zhang, F; Mu, Q; Shahsafaei, A; Hatzis, D
- July 29, 1999
Volume / Issue
- 18 / 30
Start / End Page
- 4336 - 4347
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)