Consequence of the tumor-associated conversion to cyclin D1b.

Authors

Michael A Augello, Kimmel Cancer Center, Department of Cancer Biology, Thomas Jefferson University;Follow
Lisa D Berman-Booty, Kimmel Cancer Center, Cancer Biology, Thomas Jefferson UniversityFollow
Richard Carr, Department of Biochemistry and Molecular Biology, Kimmel Cancer Center, Thomas Jefferson University,Follow
Akihiro Yoshida, Medical University of South Carolina, Hollings Cancer Center, Charleston, SC
Jeffry L Dean, Kimmel Cancer Center, Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PAFollow
M J Schiewer, Kimmel Cancer Center, Department of Cancer Biology, Thomas Jefferson UniversityFollow
Felix Y Feng, Michigan Center for Translational Pathology, University of Michigan Medical Center; Department of Radiation Oncology, University of Michigan Medical Center; Comprehensive Cancer Center, University of Michigan Medical CenterFollow
Scott A Tomlins, Michigan Center for Translational Pathology, Comprehensive Cancer Center, Department of Urology, University of Michigan Medical CenterFollow
Erhe Gao, Pharmacology and Center for Translational Medicine, Philadelphia, PA, United StatesFollow
Walter J Koch, Pharmacology and Center for Translational Medicine, Philadelphia, PA, United States ; Temple University School of MedicineFollow
Jeffrey L Benovic, Kimmel Cancer Center, Department of Biochemistry and Molecular Biology, Thomas Jefferson UniversityFollow
John Alan Diehl, Medical University of South Carolina, Hollings Cancer Center, Charleston, SC
Karen E Knudsen, Department of Radiation Oncology, Department of Urology, Kimmel Cancer Center, Department of Cancer Biology, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

5-1-2015

Comments

This article has been peer reviewed. It was published in: EMBO Molecular Medicine.

Volume 7, Issue 5, 1 May 2015, Pages 628-647.

The published version is available at DOI: 10.15252/emmm.201404242

Copyright © 2015 The Authors

Abstract

Clinical evidence suggests that cyclin D1b, a variant of cyclin D1, is associated with tumor progression and poor outcome. However, the underlying molecular basis was unknown. Here, novel models were created to generate a genetic switch from cyclin D1 to cyclin D1b. Extensive analyses uncovered overlapping but non-redundant functions of cyclin D1b compared to cyclin D1 on developmental phenotypes, and illustrated the importance of the transcriptional regulatory functions of cyclin D1b in vivo. Data obtained identify cyclin D1b as an oncogene, wherein cyclin D1b expression under the endogenous promoter induced cellular transformation and further cooperated with known oncogenes to promote tumor growth in vivo. Further molecular interrogation uncovered unexpected links between cyclin D1b and the DNA damage/PARP1 regulatory networks, which could be exploited to suppress cyclin D1b-driven tumors. Collectively, these data are the first to define the consequence of cyclin D1b expression on normal cellular function, present evidence for cyclin D1b as an oncogene, and provide pre-clinical evidence of effective methods to thwart growth of cells dependent upon this oncogenic variant.

Recommended Citation

Augello, Michael A; Berman-Booty, Lisa D; Carr, Richard; Yoshida, Akihiro; Dean, Jeffry L; Schiewer, M J; Feng, Felix Y; Tomlins, Scott A; Gao, Erhe; Koch, Walter J; Benovic, Jeffrey L; Diehl, John Alan; and Knudsen, Karen E, "Consequence of the tumor-associated conversion to cyclin D1b." (2015). Department of Cancer Biology Faculty Papers. Paper 75.
https://jdc.jefferson.edu/cbfp/75

PubMed ID

25787974