title: Calcitonin driven v-Ha-ras induces multilineage pulmonary epithelial hyperplasias and neoplasms.
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.
authors.affiliation: Children's Hospital, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Sunday
authors.forename: K J
authors.initials: KJ
authors.lastname: Haley
authors.forename: K
authors.initials: K
authors.lastname: Sikorski
authors.forename: S A
authors.initials: SA
authors.lastname: Graham
authors.forename: R L
authors.initials: RL
authors.lastname: Emanuel
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.forename: Q
authors.initials: Q
authors.lastname: Mu
authors.forename: A
authors.initials: A
authors.lastname: Shahsafaei
authors.forename: D
authors.initials: D
authors.lastname: Hatzis
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D002116:Calcitonin / Q000494:pharmacology*; D019070:Cell Lineage; D004195:Disease Models, Animal; D011905:Genes, ras / Q000235:genetics*; D006965:Hyperplasia / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018358:Neuroendocrine Tumors / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002116:Calcitonin