Cancer Research Prevention Award Advances in Breast Cancer Research
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
[Cancer Research 59, 3705-3711, August 1, 1999]
© 1999 American Association for Cancer Research
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Drissi, H.
Right arrow Articles by Stein, G. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Drissi, H.
Right arrow Articles by Stein, G. S.
[Cancer Research 59, 3705-3711, August 1, 1999]
© 1999 American Association for Cancer Research

Molecular Biology and Genetics

The Cell Cycle Regulator p27kip1 Contributes to Growth and Differentiation of Osteoblasts1

Hicham Drissi, Dennet Hushka, Fauzia Aslam, Que Nguyen, Elizabeth Buffone, Andrew Koff, André J. van Wijnen, Jane B. Lian, Janet L. Stein and Gary S. Stein2

Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655 [H. D., D. H., F. A., Q. N., E. B., A. J. v. W., J. B. L., J. L. S., G. S. S.], and Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [A. K.]

The cyclin-dependent kinase (cdk) inhibitors are key regulators of cell cycle progression. p27 and p21 are members of the Cip/Kip family of cdk inhibitors and regulate cell growth by inactivating cell cycle stage-specific CDK-cyclin complexes. Because down-regulation of osteoprogenitor proliferation is a critical step for osteoblast differentiation, we investigated expression of p27 and p21 during development of the osteoblast phenotype in rat calvarial osteoblasts and in proliferating and growth-inhibited osteosarcoma ROS 17/2.8 cells. Expression of these proteins indicates that p21, which predominates in the growth period, is related to proliferation control. p27 levels are maximal postproliferatively, suggesting a role in the transition from cell proliferation to osteoblast differentiation. We directly examined the role of p27 during differentiation of osteoprogenitor cells derived from the bone marrow (BM) of p27-/- mice. BM cells from p27 null mice exhibited increased proliferative activity compared with BM cells from wild-type mice and formed an increased number and larger size of osteoblastic colonies, which further differentiated to the mineralization stage. Although p27-/- adherent marrow cells proliferate faster, they retain competency for differentiation, which may result, in part, from observed higher p21 levels compared with wild type. Histological studies of p27-/- bones also showed an increased cellularity in the marrow cavity compared with the p27+/+. The increased proliferation in bone does not lead to tumorigenesis, in contrast to observed adenomas in the null mice. Taken together, these findings indicate that p27 plays a key role in regulating osteoblast differentiation by controlling proliferation-related events in bone cells.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
N. M. Teplyuk, M. Galindo, V. I. Teplyuk, J. Pratap, D. W. Young, D. Lapointe, A. Javed, J. L. Stein, J. B. Lian, G. S. Stein, et al.
Runx2 Regulates G Protein-coupled Signaling Pathways to Control Growth of Osteoblast Progenitors
J. Biol. Chem., October 10, 2008; 283(41): 27585 - 27597.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Z. Li, M. Q. Hassan, S. Volinia, A. J. van Wijnen, J. L. Stein, C. M. Croce, J. B. Lian, and G. S. Stein
A microRNA signature for a BMP2-induced osteoblast lineage commitment program
PNAS, September 16, 2008; 105(37): 13906 - 13911.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. Lamour, C. Detry, C. Sanchez, Y. Henrotin, V. Castronovo, and A. Bellahcene
Runx2- and Histone Deacetylase 3-mediated Repression Is Relieved in Differentiating Human Osteoblast Cells to Allow High Bone Sialoprotein Expression
J. Biol. Chem., December 14, 2007; 282(50): 36240 - 36249.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
B. M. Fischer, S. Zheng, R. Fan, and J. A. Voynow
Neutrophil elastase inhibition of cell cycle progression in airway epithelial cells in vitro is mediated by p27kip1
Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L762 - L768.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
N. Yeh, J. P. Miller, T. Gaur, T. D. Capellini, J. Nikolich-Zugich, C. de la Hoz, L. Selleri, T. G. Bromage, A. J. van Wijnen, G. S. Stein, et al.
Cooperation between p27 and p107 during Endochondral Ossification Suggests a Genetic Pathway Controlled by p27 and p130
Mol. Cell. Biol., July 15, 2007; 27(14): 5161 - 5171.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
M. Paris, W.-H. Wang, M.-H. Shin, D. S. Franklin, and O. M. Andrisani
Homeodomain Transcription Factor Phox2a, via Cyclic AMP-Mediated Activation, Induces p27Kip1 Transcription, Coordinating Neural Progenitor Cell Cycle Exit and Differentiation
Mol. Cell. Biol., December 1, 2006; 26(23): 8826 - 8839.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
H. W. Lee, J. H. Suh, A Y. Kim, Y. S. Lee, S. Y. Park, and J. B. Kim
Histone Deacetylase 1-Mediated Histone Modification Regulates Osteoblast Differentiation
Mol. Endocrinol., October 1, 2006; 20(10): 2432 - 2443.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
H. Guenou, K. Kaabeche, C. Dufour, H. Miraoui, and P. J. Marie
Down-Regulation of Ubiquitin Ligase Cbl Induced by Twist Haploinsufficiency in Saethre-Chotzen Syndrome Results in Increased PI3K/Akt Signaling and Osteoblast Proliferation
Am. J. Pathol., October 1, 2006; 169(4): 1303 - 1311.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. Cho, J. H. Kim, S. H. Back, and S. K. Jang
Polypyrimidine Tract-Binding Protein Enhances the Internal Ribosomal Entry Site-Dependent Translation of p27Kip1 mRNA and Modulates Transition from G1 to S Phase
Mol. Cell. Biol., February 15, 2005; 25(4): 1283 - 1297.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Qin, X. Li, J.-K. Ko, and N. C. Partridge
Parathyroid Hormone Uses Multiple Mechanisms to Arrest the Cell Cycle Progression of Osteoblastic Cells from G1 to S Phase
J. Biol. Chem., January 28, 2005; 280(4): 3104 - 3111.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
D. M. Thomas, S. A. Johnson, N. A. Sims, M. K. Trivett, J. L. Slavin, B. P. Rubin, P. Waring, G. A. McArthur, C. R. Walkley, A. J. Holloway, et al.
Terminal osteoblast differentiation, mediated by runx2 and p27KIP1, is disrupted in osteosarcoma
J. Cell Biol., December 6, 2004; 167(5): 925 - 934.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Sunters, D. P. Thomas, W. A. Yeudall, and A. E. Grigoriadis
Accelerated Cell Cycle Progression in Osteoblasts Overexpressing the c-fos Proto-oncogene: INDUCTION OF CYCLIN A AND ENHANCED CDK2 ACTIVITY
J. Biol. Chem., March 12, 2004; 279(11): 9882 - 9891.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Wang and M. J. Garabedian
Modulation of Glucocorticoid Receptor Transcriptional Activation, Phosphorylation, and Growth Inhibition by p27Kip1
J. Biol. Chem., December 19, 2003; 278(51): 50897 - 50901.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. J. Westendorf, S. K. Zaidi, J. E. Cascino, R. Kahler, A. J. van Wijnen, J. B. Lian, M. Yoshida, G. S. Stein, and X. Li
Runx2 (Cbfa1, AML-3) Interacts with Histone Deacetylase 6 and Represses the p21CIP1/WAF1 Promoter
Mol. Cell. Biol., November 15, 2002; 22(22): 7982 - 7992.
[Abstract] [Full Text] [PDF]

Home page
 Cell Growth Differ.Home page
T. K. Said, R. C. B. Moraes, U. Singh, F. S. Kittrell, and D. Medina
Cyclin-dependent Kinase (cdk) Inhibitors/cdk4/cdk2 Complexes in Early Stages of Mouse Mammary Preneoplasia
Cell Growth Differ., June 1, 2001; 12(6): 285 - 295.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
D. Waltregny, I. Leav, S. Signoretti, P. Soung, D. Lin, F. Merk, J. Y. Adams, N. Bhattacharya, N. Cirenei, and M. Loda
Androgen-Driven Prostate Epithelial Cell Proliferation and Differentiation in Vivo Involve the Regulation of p27
Mol. Endocrinol., May 1, 2001; 15(5): 765 - 782.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.