Abstract
The proliferation of vascular smooth muscle cells (VSMCs) plays a major role in the pathogenesis of many cardiovascular diseases. Geminin regulates DNA replication and cell cycle progression and plays a key role in the proliferation of cancer cells. We therefore hypothesized that geminin regulates the proliferation of VSMCs. The present study demonstrates that the level of geminin expression was low in quiescent VSMCs (approximately 90% and 10% of cells in the G1 and in S/G2/M phases of the cell cycle, respectively), increased as more cells entered in S/G2/M, and then decreased as cells exited S/G2/M. Further, angiotensin II and norepinephrine stimulated expression of geminin in VSMCs. However, the DNA content, nuclear morphology, percentage of cells at different stages of the cell cycle, and rate of proliferation of VSMCs from which geminin was either depleted or overexpressed were all similar. These findings indicate geminin functions differently in VSMCs than it does in cancer cell lines and that it may provide a target for treating cancers without affecting normal cells.
Article PDF
Similar content being viewed by others
References
Kawai-Kowase K, Owens G K. Multiple repressor pathways contribute to phenotypic switching of vascular smooth muscle cells. Am J Physiol Cell Physiol, 2007, 292: C59–69
Owens G K, Kumar M S, Wamhoff B R. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev, 2004, 84: 767–801
Charron T, Nili N, Strauss B H. The cell cycle: a critical therapeutic target to prevent vascular proliferative disease. Can J Cardiol, 2006, 22(Suppl B): 41B–55B
Stillman B. Cell cycle control of DNA replication. Science, 1996, 274: 1659–1664
Dutta A, Bell S P. Initiation of DNA replication in eukaryotic cells. Ann Rev Cell Dev Biol, 1997, 13: 293–332
Wohlschlegel J A, Dwyer B T, Dhar S K, et al. Inhibition of eukaryotic DNA replication by geminin binding to cdt1. Science, 2000, 290: 2309–2312
Mihaylov I S, Kondo T, Jones L, et al. Control of DNA replication and chromosome ploidy by geminin and cyclin A. Mol Cell Biol, 2002, 22: 1868–1880
McGarry T J, Kirschner M W. Geminin, an inhibitor of DNA replication, is degraded during mitosis. Cell, 1998, 93: 1043–1053
Zhu W, Chen Y, Dutta A. Rereplication by depletion of geminin is seen regardless of p53 status and activates a G2/M checkpoint. Mol Cell Biol, 2004, 24: 7140–7150
Melixetian M, Ballabeni A, Masiero L, et al. Loss of geminin induces rereplication in the presence of functional p53. J Cell Biol, 2004, 165: 473–482
Montanari M, Boninsegna A, Faraglia B, et al. Increased expression of geminin stimulates the growth of mammary epithelial cells and is a frequent event in human tumors. J Cell Physiol, 2005, 202: 215–222
Wohlschlegel J A, Kutok J L, Weng A P, et al. Expression of geminin as a marker of cell proliferation in normal tissues and malignancies. Am J Pathol, 2002, 161: 267–273
Eward K L, Obermann E C, Shreeram S, et al. DNA replication licensing in somatic and germ cells. J Cell Sci, 2004, 117: 5875–5886
Montanari M, Macaluso M, Cittadini A, et al. Role of geminin: from normal control of DNA replication to cancer formation and progression? Cell Death Diff, 2006, 13: 1052–1056
Pang X, Sun N L. Calcineurin-NFAT signaling is involved in phenylephrine-induced vascular smooth muscle cell proliferation. Acta Pharmacol Sin, 2009, 30: 537–544
Gonzalez M A, Tachibana K E, Chin S F, et al. Geminin predicts adverse clinical outcome in breast cancer by reflecting cell-cycle progression. J Pathol, 2004, 204: 121–130
Fujita M. Cdt1 revisited: complex and tight regulation during the cell cycle and consequences of deregulation in mammalian cells. Cell Div, 2006, 1: 22
Nishihara K, Shomori K, Tamura T, et al. Immunohistochemical expression of geminin in colorectal cancer: implication of prognostic significance. Oncol Rep, 2009, 21: 1189–1195
Author information
Authors and Affiliations
Corresponding author
Additional information
This article is published with open access at Springerlink.com
Electronic supplementary material
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Guo, J., Sun, N. Cell cycle regulator geminin is dispensable for the proliferation of vascular smooth muscle cells. Sci. China Life Sci. 56, 731–738 (2013). https://doi.org/10.1007/s11427-013-4513-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-013-4513-1