Cyclin-dependent kinase inhibitor expression in pulmonary Clara cells transformed with SV40 large T antigen in transgenic mice.
Expression of cell cycle regulatory genes in mouse lung was investigated in transgenic models for Clara cell transformation. Clara cells were transformed by generating transgenic mice in which the SV40 large T antigen was expressed under the control of the mouse Clara cell M(r) 10,000 protein promoter. The resulting lung tumors express the large T antigen in normal Clara cells and in tumors, and these tumors express reduced levels of CC10 mRNA. The expression of cell cycle regulatory protein, p53, and the cyclin-dependent kinase inhibitors was analyzed by Northern blot analysis and in situ hybridization throughout the progression of Clara cell transformation in the lung. Increases in specific cyclin-dependent kinase inhibitor steady-state mRNA levels were detected in p15, p18, p27, and p57 during tumor progression. The expression of p15, p57, and p21 mRNAs were verified by in situ hybridization. Using this approach, regulatory genes have been identified that may be involved in the regulation of Clara cell differentiation.
Magdaleno
S M
SM
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Wang
G
G
Mireles
V L
VL
Ray
M K
MK
Finegold
M J
MJ
DeMayo
F J
FJ
D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000737:chemistry; D002454:Cell Differentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D002472:Cell Transformation, Viral / Q000235:genetics*; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic
D000952:Antigens, Polyomavirus Transforming; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D018844:Cyclin-Dependent Kinases