Carcinogenesis, Vol 18, 2063-2069, Copyright © 1997 by Oxford University Press
ZM Mu, XF Le, S Vallian, AB Glassman and KS Chang
Our previous studies demonstrated that PML is a growth suppressor that
suppresses oncogenic transformation of NIH/3T3 cells and rat embryo
fibroblasts. PML is a nuclear matrix-associated phosphoprotein whose
expression is regulated during the cell cycle. Disruption of PML function
by t(15;17) in acute promyelocytic leukemia (APL) plays a critical role in
leukemogenesis. To further study the role of PML in the control of cell
growth, we have stably overexpressed PML protein in the HeLa cell line.
This overexpression of PML significantly reduced the growth rate of HeLa
cells and suppressed anchorage-independent growth in soft agar. We
consequently investigated several parameters correlated with cell growth
and cell cycle progression. We found that, in comparison with the parental
HeLa cells, HeLa/PML stable clones showed proportionally more cells in G1
phase, fewer cells in S phase and about the same number in G2/M phase. The
HeLa/PML clones showed a significantly longer doubling time as a result of
a lengthening of the G1 phase. No effect on apoptosis was found in HeLa
cells overexpressing PML. This observation indicates that PML suppresses
cell growth by increasing cell cycle duration as a result of G1 elongation.
To further understand the mechanism of the effect of PML on HeLa cells,
expression of cell cycle-related proteins in HeLa/PML and parental HeLa
cells was analyzed. We found that Rb phosphorylation was significantly
reduced in PML stable clones. Expression of cyclin E, Cdk2 and p27 proteins
was also significantly reduced. These studies indicate that PML affects
cell cycle progression by mediating expression of several key proteins that
normally control cell cycle progression. These results further extend our
current understanding of PML function in human cells and its important role
in cell cycle regulation.
ARTICLES
Stable overexpression of PML alters regulation of cell cycle progression in HeLa cells
Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J.-P. Lalonde, R. Lim, E. Ingley, P. A. Tilbrook, M. J. Thompson, R. McCulloch, J. G Beaumont, C. Wicking, H. J. Eyre, G. R. Sutherland, et al. HLS5, a Novel RBCC (Ring Finger, B Box, Coiled-coil) Family Member Isolated from a Hemopoietic Lineage Switch, Is a Candidate Tumor Suppressor J. Biol. Chem., February 27, 2004; 279(9): 8181 - 8189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-X. Xu, R.-X. Zhao, T. Ding, T. T. Tran, W. Zhang, P. P. Pandolfi, and K.-S. Chang Promyelocytic Leukemia Protein 4 Induces Apoptosis by Inhibition of Survivin Expression J. Biol. Chem., January 16, 2004; 279(3): 1838 - 1844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-X. Xu, A. Timanova-Atanasova, R.-X. Zhao, and K.-S. Chang PML Colocalizes with and Stabilizes the DNA Damage Response Protein TopBP1 Mol. Cell. Biol., June 15, 2003; 23(12): 4247 - 4256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Shpargel, J. K. Ospina, K. E. Tucker, A. G. Matera, and M. D. Hebert Control of Cajal body number is mediated by the coilin C-terminus J. Cell Sci., January 15, 2003; 116(2): 303 - 312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-S. Wu, Z.-X. Xu, and K.-S. Chang The Promyelocytic Leukemia Protein Represses A20-mediated Transcription J. Biol. Chem., August 23, 2002; 277(35): 31734 - 31739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wienzek and M. Dobbelstein Viral and Cellular Factors That Target the Promyelocytic Leukemia Oncogenic Domains Strongly Activate a Glucocorticoid-Responsive Promoter J. Virol., June 1, 2001; 75(11): 5391 - 5397. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. Liao, X. Y. Wang, H. Q. Wei, S. Q. Li, T. Merghoub, P. P. Pandolfi, and D. J. Wolgemuth Altered myelopoiesis and the development of acute myeloid leukemia in transgenic mice overexpressing cyclin A1 PNAS, May 24, 2001; (2001) 121540098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-S. Wu, S. Vallian, E. Seto, W.-M. Yang, D. Edmondson, S. Roth, and K.-S. Chang The Growth Suppressor PML Represses Transcription by Functionally and Physically Interacting with Histone Deacetylases Mol. Cell. Biol., April 1, 2001; 21(7): 2259 - 2268. [Abstract] [Full Text]
|
|
|
|
|
|
J. Burkham, D. M. Coen, C. B. C. Hwang, and S. K. Weller Interactions of Herpes Simplex Virus Type 1 with ND10 and Recruitment of PML to Replication Compartments J. Virol., March 1, 2001; 75(5): 2353 - 2367. [Abstract] [Full Text]
|
|
|
|
|
|
H. Li, C. Leo, J. Zhu, X. Wu, J. O'Neil, E.-J. Park, and J. D. Chen Sequestration and Inhibition of Daxx-Mediated Transcriptional Repression by PML Mol. Cell. Biol., March 1, 2000; 20(5): 1784 - 1796. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Melnick and J. D. Licht Deconstructing a Disease: RAR{alpha}, Its Fusion Partners, and Their Roles in the Pathogenesis of Acute Promyelocytic Leukemia Blood, May 15, 1999; 93(10): 3167 - 3215. [Full Text] [PDF]
|
|
|
|
 |
|
 R. DONNELLAN and R. CHETTY Cyclin E in human cancers FASEB J, May 1, 1999; 13(8): 773 - 780. [Abstract] [Full Text]
|
|
|
|
|
|
M. Nevels, B. Täuber, E. Kremmer, T. Spruss, H. Wolf, and T. Dobner Transforming Potential of the Adenovirus Type 5 E4orf3 Protein J. Virol., February 1, 1999; 73(2): 1591 - 1600. [Abstract] [Full Text]
|
|
|
|
|
|
S. Vallian, K.-V. Chin, and K.-S. Chang The Promyelocytic Leukemia Protein Interacts with Sp1 and Inhibits Its Transactivation of the Epidermal Growth Factor Receptor Promoter Mol. Cell. Biol., December 1, 1998; 18(12): 7147 - 7156. [Abstract] [Full Text]
|
|
|
|
|
|
C. Liao, X. Y. Wang, H. Q. Wei, S. Q. Li, T. Merghoub, P. P. Pandolfi, and D. J. Wolgemuth Altered myelopoiesis and the development of acute myeloid leukemia in transgenic mice overexpressing cyclin A1 PNAS, June 5, 2001; 98(12): 6853 - 6858. [Abstract] [Full Text] [PDF]
|
|