This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xia, F. Articles by Altieri, D. C. Search for Related Content PubMed PubMed Citation Articles by Xia, F. Articles by Altieri, D. C.

Mitosis-Independent Survivin Gene Expression In vivo and Regulation by p53

Department of Cancer Biology and the Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts

Requests for reprints: Dario C. Altieri, Department of Cancer Biology, LRB428, 364 Plantation Street, Worcester, MA 01605. Phone: 508-856-5775; Fax: 508-856-5792; E-mail: dario.altieri{at}umassmed.edu.

Survivin is an essential mitotic gene, and this has been speculated to reflect its primary function in development and cancer. Here, we generated a knock-in transgenic mouse (SVVp-GFP) in which a green fluorescent protein (GFP) reporter gene was placed under the control of the survivin promoter that regulates transcription at mitosis. The expression of endogenous survivin was widespread in mouse tissues during development and shortly after birth. In contrast, GFP reactivity was undetectable in transgenic mouse embryos, and was largely limited postnatally to mitotic cells in the testes. Double transgenic mice generated in the tumor-prone Min/+ background exhibited intestinal adenomas that strongly expressed endogenous survivin, but only isolated GFP-positive cells. Conversely, dysplastic adenomas (16%) stained intensely for GFP, and revealed focal reactivity for mutant, but not wild-type, p53. The expression of GFP was increased by 10-fold in p53^–/– as opposed to p53^+/+ HCT116 colorectal cancer cells, and reintroduction of p53 in p53^–/– cells abolished GFP expression. Therefore, the mitotic transcription of the survivin gene is highly restricted in vivo, and unexpectedly negatively regulated by p53. Contrary to a commonly held view, the dominant function(s) of survivin in development and tumor ontogeny are largely cell cycle–independent. (Cancer Res 2006; (66)7: 3392-5)

This article has been cited by other articles:

				M. Guha, J. Plescia, I. Leav, J. Li, L. R. Languino, and D. C. Altieri Endogenous Tumor Suppression Mediated by PTEN Involves Survivin Gene Silencing Cancer Res., June 15, 2009; 69(12): 4954 - 4958. [Abstract] [Full Text] [PDF]

				C. W. Lee, C. M. Raskett, I. Prudovsky, and D. C. Altieri Molecular Dependence of Estrogen Receptor-Negative Breast Cancer on a Notch-Survivin Signaling Axis Cancer Res., July 1, 2008; 68(13): 5273 - 5281. [Abstract] [Full Text] [PDF]

				D. Raj, T. Liu, G. Samadashwily, F. Li, and D. Grossman Survivin repression by p53, Rb and E2F2 in normal human melanocytes Carcinogenesis, January 1, 2008; 29(1): 194 - 201. [Abstract] [Full Text] [PDF]

				J. Thomas, T. Liu, M. A. Cotter, S. R. Florell, K. Robinette, A. N. Hanks, and D. Grossman Melanocyte Expression of Survivin Promotes Development and Metastasis of UV-Induced Melanoma in HGF-Transgenic Mice Cancer Res., June 1, 2007; 67(11): 5172 - 5178. [Abstract] [Full Text] [PDF]

				M. Pennati, M. Folini, and N. Zaffaroni Targeting survivin in cancer therapy: fulfilled promises and open questions Carcinogenesis, June 1, 2007; 28(6): 1133 - 1139. [Abstract] [Full Text] [PDF]