Increased expression of geminin stimulates the growth of mammary epithelial cells and is a frequent event in human tumors
Version of Record online: 5 AUG 2004
Copyright © 2005 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 202, Issue 1, pages 215–222, January 2005
How to Cite
Montanari, M., Boninsegna, A., Faraglia, B., Coco, C., Giordano, A., Cittadini, A. and Sgambato, A. (2005), Increased expression of geminin stimulates the growth of mammary epithelial cells and is a frequent event in human tumors. J. Cell. Physiol., 202: 215–222. doi: 10.1002/jcp.20120
- Issue online: 28 OCT 2004
- Version of Record online: 5 AUG 2004
- Manuscript Accepted: 15 MAR 2004
- Manuscript Received: 6 MAR 2004
- Università Cattolica (MURST 60%)
- Compagnia di San Paolo and Associazione Italiana per la Ricerca sul Cancro (AIRC)
Geminin is a potent inhibitor of origin assembly and re-replication in multicellular eukaryotes and is a negative regulator of DNA replication during the cell cycle. Thus, it was proposed as an inhibitor of cell proliferation and as a potential tumor suppressor gene. However, the protein was found specifically expressed in proliferating lymphocytes and epithelial cells and up-regulated in several malignancies. Therefore, geminin is now regarded as an oncogene but its role in tumor development remains unknown. In this study, we evaluated by Western blot analysis the expression of geminin in a series of human cancer cell lines of various histogenetic origin and in a series of human primary colon, rectal, and breast cancers. Expression of geminin was variable in different cell lines and not related to the expression level of the corresponding mRNA. Moreover, geminin was expressed at higher level in 56% and 58% of colon and rectal cancers, respectively, compared with the corresponding adjacent normal mucosa. A high expression of geminin was also detected by immunohistochemistry in 60% of human primary breast cancers. We also transfected a full-length geminin cDNA in a human non-tumorigenic and a cancer breast cell lines and obtained derivatives expressing high levels of the protein. Geminin overexpression stimulated cell cycle progression and proliferation in both normal and cancer cells and increased the anchorage—independent growth of breast cancer cells. These results demonstrate that expression of geminin is frequently deregulated in tumor cells and might play an important role in the regulation of cell growth in both normal and malignant cells. © 2005 Wiley-Liss, Inc.