Calcitonin driven v-Ha-ras induces multilineage pulmonary epithelial hyperplasias and neoplasms.
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
M E
ME
Children's Hospital, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Haley
K J
KJ
Sikorski
K
K
Graham
S A
SA
Emanuel
R L
RL
Zhang
F
F
Mu
Q
Q
Shahsafaei
A
A
Hatzis
D
D
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
D002116:Calcitonin