Mice injected with urethane develop tumors with distinct histological patte
rns, which are classified as solid, papillary, or a mixture of these two pa
tterns within the same tumor. Most investigators agree that solid tumors ar
ise from alveolar type II cells, but the cellular origin of papillary tumor
s is less certain, being attributed to either type II cells or nonciliated
bronchiolar epithelial (Clara) cells. To characterize the state of differen
tiation of these tumors more precisely and to provide additional informatio
n on gene expression, we used immunocytochemistry and/or in situ hybridizat
ion to determine the cellular localization of surfactant-associated protein
s A (SP-A), SP-B, SP-C, and SP-D; Clara cell-associated protein CC-10; and
thyroid transcription factor-1. In normal mouse lung, the messenger RNAs (m
RNAs) for SP-A, SP-B, and SP-D were expressed in both type II cells and Cla
ra cells. SP-C mRNA, however, was expressed only in type II cells, and CC-1
0 expression of mRNA was restricted to Clara cells. All tumors examined, bo
th solid and papillary, expressed SP-A, SP-B, SP-C, SP-D, and thyroid trans
cription factor-1, but not CC-10, However, SP-C expression was slightly dim
inished in larger (older) papillary tumors. These results demonstrate that
urethane-induced murine lung tumors express the type II cell phenotype.