Cyclin D1 as a proliferative marker regulating retinoblastoma phosphorylation in mouse lung epithelial cells

Cynthia L. Mamay, Irene E. Schauer, Pamela L. Rice, Lori D. Dwyer-Nield, Ming You, Robert A. Sclafani, Alvin M. Malkinson

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)165-172
Number of pages8
JournalCancer Letters
Volume168
Issue number2
DOIs
StatePublished - Jul 26 2001

Keywords

  • Cyclin D1
  • Mouse lung epithelial cells
  • Proliferative marker
  • Retinoblastoma phosphorylation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Cyclin D1 as a proliferative marker regulating retinoblastoma phosphorylation in mouse lung epithelial cells'. Together they form a unique fingerprint.

Cite this