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 Zhang, T. Articles by Boman, B. M. Search for Related Content PubMed PubMed Citation Articles by Zhang, T. Articles by Boman, B. M.

Evidence That APC Regulates Survivin Expression

A Possible Mechanism Contributing to the Stem Cell Origin of Colon Cancer

Division of Genetic and Preventive Medicine [T. Z., T. O., Zhe. G., Zhi. G., S. M. E., B. M. B.] and Kimmel Cancer Center [B. M. B.], Thomas Jefferson University, Philadelphia, PA 19107; CA^*TX Inc., Gladwyne, Pennsylvania 19035 [J. Z. F.]

Because colorectal cancers (CRCs) frequently display APC mutation, inhibition of apoptosis, and increased expression of the antiapoptotic protein survivin, we hypothesized that APC mutation inhibits apoptosis by allowing constitutive survivin expression. Using HT-29 CRC cell lines having inducible wild-type APC (wt-APC) or transfected dominant-negative TCF-4, we show that wt-APC down-regulates survivin expression via APC/ß-catenin/TCF-4 signaling. Using normal colonic epithelium, we found survivin by immunostaining/reverse transcription-PCR to be preferentially expressed in the lower crypt (which inversely correlates with wt-APC’s expression pattern). Thus, wt-APC, by progressively decreasing survivin and increasing apoptosis from crypt bottom to top, may limit the population size of stem cells and other proliferative cells in the lower crypt; mutant APC may allow expansion of these populations, thereby initiating tumorigenesis.

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]

				E. H. Huang, M. J. Hynes, T. Zhang, C. Ginestier, G. Dontu, H. Appelman, J. Z. Fields, M. S. Wicha, and B. M. Boman Aldehyde Dehydrogenase 1 Is a Marker for Normal and Malignant Human Colonic Stem Cells (SC) and Tracks SC Overpopulation during Colon Tumorigenesis Cancer Res., April 15, 2009; 69(8): 3382 - 3389. [Abstract] [Full Text] [PDF]

				D. A. Rodriguez, J. C. Tapia, J. G. Fernandez, V. A. Torres, N. Munoz, D. Galleguillos, L. Leyton, and A. F. G. Quest Caveolin-1-mediated Suppression of Cyclooxygenase-2 via a {beta}-catenin-Tcf/Lef-dependent Transcriptional Mechanism Reduced Prostaglandin E2 Production and Survivin Expression Mol. Biol. Cell, April 15, 2009; 20(8): 2297 - 2310. [Abstract] [Full Text] [PDF]

				V. A. de Jesus Perez, T.-P. Alastalo, J. C. Wu, J. D. Axelrod, J. P. Cooke, M. Amieva, and M. Rabinovitch Bone morphogenetic protein 2 induces pulmonary angiogenesis via Wnt-{beta}-catenin and Wnt-RhoA-Rac1 pathways J. Cell Biol., January 12, 2009; 184(1): 83 - 99. [Abstract] [Full Text] [PDF]

				A. C. Mita, M. M. Mita, S. T. Nawrocki, and F. J. Giles Survivin: Key Regulator of Mitosis and Apoptosis and Novel Target for Cancer Therapeutics Clin. Cancer Res., August 15, 2008; 14(16): 5000 - 5005. [Abstract] [Full Text] [PDF]

				A. M. Roccaro, X. Leleu, A. Sacco, A.-S. Moreau, E. Hatjiharissi, X. Jia, L. Xu, B. Ciccarelli, C. J. Patterson, H. T. Ngo, et al. Resveratrol Exerts Antiproliferative Activity and Induces Apoptosis in Waldenstrom's Macroglobulinemia Clin. Cancer Res., March 15, 2008; 14(6): 1849 - 1858. [Abstract] [Full Text] [PDF]

				V. A. Torres, J. C. Tapia, D. A. Rodriguez, A. Lladser, C. Arredondo, L. Leyton, and A. F. G. Quest E-Cadherin Is Required for Caveolin-1-Mediated Down-Regulation of the Inhibitor of Apoptosis Protein Survivin via Reduced {beta}-Catenin-Tcf/Lef-Dependent Transcription Mol. Cell. Biol., November 1, 2007; 27(21): 7703 - 7717. [Abstract] [Full Text] [PDF]

				P. Lechler, X. Wu, W. Bernhardt, V. Campean, S. Gastiger, T. Hackenbeck, B. Klanke, A. Weidemann, C. Warnecke, K. Amann, et al. The Tumor Gene Survivin Is Highly Expressed in Adult Renal Tubular Cells: Implications for a Pathophysiological Role in the Kidney Am. J. Pathol., November 1, 2007; 171(5): 1483 - 1498. [Abstract] [Full Text] [PDF]

				J. N. Rich Cancer Stem Cells in Radiation Resistance Cancer Res., October 1, 2007; 67(19): 8980 - 8984. [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]

				A A Borbely, M Murvai, K Szarka, J Konya, L Gergely, Z Hernadi, and G Veress Survivin promoter polymorphism and cervical carcinogenesis J. Clin. Pathol., March 1, 2007; 60(3): 303 - 306. [Abstract] [Full Text] [PDF]

				P.-O. Esteve, H. G. Chin, and S. Pradhan Molecular Mechanisms of Transactivation and Doxorubicin-mediated Repression of survivin Gene in Cancer Cells J. Biol. Chem., January 26, 2007; 282(4): 2615 - 2625. [Abstract] [Full Text] [PDF]

				Y. Feng, G. T. Bommer, Y. Zhai, A. Akyol, T. Hinoi, I. Winer, H. V. Lin, K. M. Cadigan, K. R. Cho, and E. R. Fearon Drosophila split ends Homologue SHARP Functions as a Positive Regulator of Wnt/{beta}-Catenin/T-Cell Factor Signaling in Neoplastic Transformation Cancer Res., January 15, 2007; 67(2): 482 - 491. [Abstract] [Full Text] [PDF]

				A. Marconi, K. Dallaglio, R. Lotti, C. Vaschieri, F. Truzzi, F. Fantini, and C. Pincelli Survivin Identifies Keratinocyte Stem Cells and Is Downregulated by Anti-{beta}1 Integrin During Anoikis Stem Cells, January 1, 2007; 25(1): 149 - 155. [Abstract] [Full Text] [PDF]

				K. W. Yip, W. Shi, M. Pintilie, J. D. Martin, J. D. Mocanu, D. Wong, C. MacMillan, P. Gullane, B. O'Sullivan, C. Bastianutto, et al. Prognostic Significance of the Epstein-Barr Virus, p53, Bcl-2, and Survivin in Nasopharyngeal Cancer. Clin. Cancer Res., October 1, 2006; 12(19): 5726 - 5732. [Abstract] [Full Text] [PDF]

				X. Huang and B. Guo Adenomatous polyposis coli determines sensitivity to histone deacetylase inhibitor-induced apoptosis in colon cancer cells. Cancer Res., September 15, 2006; 66(18): 9245 - 9251. [Abstract] [Full Text] [PDF]

				S. C.M. Martinico, S. Jezzard, N. J. H. Sturt, G. Michils, S. Tejpar, R. K. Phillips, and G. Vassaux Assessment of Endostatin Gene Therapy for Familial Adenomatous Polyposis-Related Desmoid Tumors Cancer Res., August 15, 2006; 66(16): 8233 - 8240. [Abstract] [Full Text] [PDF]

				F. Li and M. G. Brattain Role of the SurvivinGene in Pathophysiology Am. J. Pathol., July 1, 2006; 169(1): 1 - 11. [Abstract] [Full Text] [PDF]

				N. Zhu, L. Gu, H. W. Findley, C. Chen, J.-T. Dong, L. Yang, and M. Zhou KLF5 Interacts with p53 in Regulating Survivin Expression in Acute Lymphoblastic Leukemia J. Biol. Chem., May 26, 2006; 281(21): 14711 - 14718. [Abstract] [Full Text] [PDF]

				H.-L. Hsiao, W.-S. Wang, P.-M. Chen, and Y. Su Overexpression of thymosin {beta}-4 renders SW480 colon carcinoma cells more resistant to apoptosis triggered by FasL and two topoisomerase II inhibitors via downregulating Fas and upregulating Survivin expression, respectively Carcinogenesis, May 1, 2006; 27(5): 936 - 944. [Abstract] [Full Text] [PDF]

				V. A. Torres, J. C. Tapia, D. A. Rodriguez, M. Parraga, P. Lisboa, M. Montoya, L. Leyton, and A. F. G. Quest Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein survivin J. Cell Sci., May 1, 2006; 119(9): 1812 - 1823. [Abstract] [Full Text] [PDF]

				D. C. Altieri Targeted therapy by disabling crossroad signaling networks: the survivin paradigm. Mol. Cancer Ther., March 1, 2006; 5(3): 478 - 482. [Abstract] [Full Text] [PDF]

				H. Takeuchi, J. Kim, A. Fujimoto, N. Umetani, T. Mori, A. Bilchik, R. Turner, A. Tran, C. Kuo, and D. S.B. Hoon X-Linked Inhibitor of Apoptosis Protein Expression Level in Colorectal Cancer Is Regulated by Hepatocyte Growth Factor/C-Met Pathway via Akt Signaling Clin. Cancer Res., November 1, 2005; 11(21): 7621 - 7628. [Abstract] [Full Text] [PDF]

				J. Park, Y. Hu, T. V. S. Murthy, F. Vannberg, B. Shen, A. Rolfs, J. E. Hutti, L. C. Cantley, J. LaBaer, E. Harlow, et al. Building a human kinase gene repository: Bioinformatics, molecular cloning, and functional validation PNAS, June 7, 2005; 102(23): 8114 - 8119. [Abstract] [Full Text] [PDF]

				A. Gregorieff and H. Clevers Wnt signaling in the intestinal epithelium: from endoderm to cancer Genes & Dev., April 15, 2005; 19(8): 877 - 890. [Abstract] [Full Text] [PDF]

				B. M. Boman, R. Walters, J. Z. Fields, A. J. Kovatich, T. Zhang, G. A. Isenberg, S. D. Goldstein, and J. P. Palazzo Colonic Crypt Changes during Adenoma Development in Familial Adenomatous Polyposis: Immunohistochemical Evidence for Expansion of the Crypt Base Cell Population Am. J. Pathol., November 1, 2004; 165(5): 1489 - 1498. [Abstract] [Full Text] [PDF]

				M. Iurlaro, F. Demontis, M. Corada, L. Zanetta, C. Drake, M. Gariboldi, S. Peiro, A. Cano, P. Navarro, A. Cattelino, et al. VE-Cadherin Expression and Clustering Maintain Low Levels of Survivin in Endothelial Cells Am. J. Pathol., July 1, 2004; 165(1): 181 - 189. [Abstract] [Full Text] [PDF]

				S. J. Kim, S. Cheung, and M. K. Hellerstein Isolation of nuclei from label-retaining cells and measurement of their turnover rates in rat colon Am J Physiol Cell Physiol, June 1, 2004; 286(6): C1464 - C1473. [Abstract] [Full Text] [PDF]

				T. Zhang, J. Z. Fields, S. M. Ehrlich, and B. M. Boman The Chemopreventive Agent Sulindac Attenuates Expression of the Antiapoptotic Protein Survivin in Colorectal Carcinoma Cells J. Pharmacol. Exp. Ther., February 1, 2004; 308(2): 434 - 437. [Abstract] [Full Text] [PDF]

				M. G. Daidone, A. Costa, M. Frattini, D. Balestra, L. Bertario, M. A. Pierotti, B. M. Boman, T. Zhang, and J. Z. Fields Correspondence re: T. Zhang et al., Evidence That APC Regulates Survivin Expression: A Possible Mechanism Contributing to the Stem Cell Origin of Colon Cancer. Cancer Res., 61: 8664-8667, 2001. Cancer Res., January 15, 2004; 64(2): 776 - 779. [Full Text] [PDF]

				V. Pisarev, B. Yu, R. Salup, S. Sherman, D. C. Altieri, and D. I. Gabrilovich Full-Length Dominant-Negative Survivin for Cancer Immunotherapy Clin. Cancer Res., December 15, 2003; 9(17): 6523 - 6533. [Abstract] [Full Text] [PDF]

				C. Doglioni, S. Piccinin, S. Demontis, M. G. Cangi, L. Pecciarini, C. Chiarelli, M. Armellin, T. Vukosavljevic, M. Boiocchi, and R. Maestro Alterations of {beta}-Catenin Pathway in Non-Melanoma Skin Tumors: Loss of {alpha}-ABC Nuclear Reactivity Correlates with the Presence of {beta}-Catenin Gene Mutation Am. J. Pathol., December 1, 2003; 163(6): 2277 - 2287. [Abstract] [Full Text]

				C. Tanaka, K. Uzawa, T. Shibahara, H. Yokoe, H. Noma, and H. Tanzawa Expression of an Inhibitor of Apoptosis, Survivin, in Oral Carcinogenesis Journal of Dental Research, August 1, 2003; 82(8): 607 - 611. [Abstract] [Full Text] [PDF]

				N. S. Williams, R. B. Gaynor, S. Scoggin, U. Verma, T. Gokaslan, C. Simmang, J. Fleming, D. Tavana, E. Frenkel, and C. Becerra Identification and Validation of Genes Involved in the Pathogenesis of Colorectal Cancer Using cDNA Microarrays and RNA Interference Clin. Cancer Res., March 1, 2003; 9(3): 931 - 946. [Abstract] [Full Text] [PDF]