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

Oncogene. 1999 Jul 29;18(30):4336-47. doi: 10.1038/sj.onc.1202810.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / metabolism
  • Animals
  • Animals, Genetically Modified
  • Calcitonin / pharmacology*
  • Cell Lineage*
  • Disease Models, Animal
  • Genes, ras / genetics*
  • Hyperplasia / genetics*
  • Immunohistochemistry
  • In Situ Hybridization
  • Lung / pathology*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Inbred C57BL
  • Neuroendocrine Tumors / genetics
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / pathology
  • Promoter Regions, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Calcitonin