| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA; Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA
2 Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA; Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA
3 Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA; Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA; Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA
* To whom correspondence should be addressed. E-mail: jwang{at}smail.umaryland.edu.
The nuclear protein c-Myc is a transcription factor involved in the control of cell cycle. Our previous studies indicate that cellular polyamines are absolutely required for cell proliferation in the crypts of small intestinal mucosa and that polyamines have the ability to stimulate expression of the c-Myc gene. The current study went further to determine whether induced nuclear c-Myc plays a role in the stimulation of cell proliferation by polyamines in intestinal crypt cells (IEC-6 line). Exposure of normal quiescent cells after 24 h serum deprivation to 5% dialyzed fetal bovine serum (dFBS) increased both cellular polyamines and expression of the c-Myc gene. Increased c-Myc protein formed heterodimers with its binding partner, Max, and specifically bound to the Myc/Max binding site, which was associated with an increase in DNA synthesis. Depletion of cellular polyamines by pretreatment with 
-difluoromethylornithine (DFMO) prevented increases in c-Myc expression and DNA synthesis induced by 5% dFBS. c-Myc gene transcription and cell proliferation decreased in polyamine-deficient cells, while the natural polyamine spermidine given together with DFMO maintained c-Myc gene expression and cell growth at normal levels. The disruption of c-Myc expression by using specific c-Myc antisense oligomers not only inhibited normal cell growth (without DFMO) but also prevented the restoration of cell proliferation by spermidine in polyamine-deficient cells. Ectopic expression of the wild-type c-Myc by the recombinant adenoviral vector containing c-Myc cDNA increased cell growth. These results indicate that polyamine-induced nuclear c-Myc interacts with Max, binds to the specific DNA sequence and plays an important role in the stimulation of normal intestinal epithelial cell proliferation.
This article has been cited by other articles:
|
|
 |
|
  L. Liu, X. Guo, J. N. Rao, T. Zou, L. Xiao, T. Yu, J. A. Timmons, D. J. Turner, and J.-Y. Wang Polyamines regulate E-cadherin transcription through c-Myc modulating intestinal epithelial barrier function Am J Physiol Cell Physiol, April 1, 2009; 296(4): C801 - C810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Seno, H. Miyoshi, S. L. Brown, M. J. Geske, M. Colonna, and T. S. Stappenbeck Efficient colonic mucosal wound repair requires Trem2 signaling PNAS, January 6, 2009; 106(1): 256 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chen, J. N. Rao, T. Zou, L. Liu, B. S. Marasa, L. Xiao, X. Zeng, D. J. Turner, and J.-Y. Wang Polyamines are required for expression of Toll-like receptor 2 modulating intestinal epithelial barrier integrity Am J Physiol Gastrointest Liver Physiol, September 1, 2007; 293(3): G568 - G576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kaneko, E. Okuda-Ashitaka, A. Ando, K. Nishimura, K. Igarashi, M. Maeda, K. Furuta, M. Suzuki, M. Matsumura, and S. Ito Polyamines upregulate the mRNA expression of cationic amino acid transporter-1 in human retinal pigment epithelial cells Am J Physiol Cell Physiol, August 1, 2007; 293(2): C729 - C737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-H. Zhang, J. N. Rao, T. Zou, L. Liu, B. S. Marasa, L. Xiao, J. Chen, D. J. Turner, and J.-Y. Wang p53-Dependent NDRG1 expression induces inhibition of intestinal epithelial cell proliferation but not apoptosis after polyamine depletion Am J Physiol Cell Physiol, July 1, 2007; 293(1): C379 - C389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Rao, O. Platoshyn, V. A. Golovina, L. Liu, T. Zou, B. S. Marasa, D. J. Turner, J. X.-J. Yuan, and J.-Y. Wang TRPC1 functions as a store-operated Ca2+ channel in intestinal epithelial cells and regulates early mucosal restitution after wounding Am J Physiol Gastrointest Liver Physiol, April 1, 2006; 290(4): G782 - G792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Zou, J. N. Rao, L. Liu, B. S. Marasa, K. M. Keledjian, A.-H. Zhang, L. Xiao, B. L. Bass, and J.-Y. Wang Polyamine depletion induces nucleophosmin modulating stability and transcriptional activity of p53 in intestinal epithelial cells Am J Physiol Cell Physiol, September 1, 2005; 289(3): C686 - C696. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
