Cyclin D1 as a proliferative marker regulating retinoblastoma phosphorylation in mouse lung epithelial cells. Cancer Lett 2001 Jul 26;168(2):165-72
Date
06/19/2001Pubmed ID
11403921DOI
10.1016/s0304-3835(01)00480-3Scopus ID
2-s2.0-0035954828 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
Elevations in cyclin D1 content increase the phosphorylation status of retinoblastoma (Rb) protein to encourage cell cycle transit. We sought to determine if cyclin D1 content could be used as an index of cell proliferation in mouse lung epithelia following growth manipulations in vitro and in vivo. Rb protein concentration was high in 82-132 and LM2, two fast-growing neoplastic mouse lung epithelial cell lines. The hyperphosphorylated form of Rb predominated in these two cell lines, while Rb in slower-growing cell lines was predominantly hypophosphorylated. Consistent with this, more cyclin D1 protein was expressed in the fast-growing cell lines than in slower-growing cells. We therefore tested whether cyclin D1 content varied with growth status. The amount of cyclin D1 decreased upon serum removal coincident with growth inhibition and then increased upon serum re-addition which stimulated resumption of proliferation. This correlation between cyclin D1 content and growth status also occurred in vivo. Cyclin D1 content increased when lungs underwent compensatory hyperplasia following damage caused by butylated hydroxytoluene administration to mice and in lung tumor extracts as compared with extracts prepared from uninvolved tissue or control lungs. We conclude that elevated cyclin D1 levels account, at least in part, for the hyperphosphorylation of Rb in neoplastic lung cells, and are associated with enhanced lung growth in vitro and in vivo.
Author List
Mamay CL, Schauer IE, Rice PL, McDoniels-Silvers A, Dwyer-Nield LD, You M, Sclafani RA, Malkinson AMMESH terms used to index this publication - Major topics in bold
AnimalsBiomarkers
Cell Division
Cell Line
Cyclin D1
Epithelial Cells
Lung
Male
Mice
Mice, Inbred BALB C
Phosphorylation
Retinoblastoma Protein