![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
RESEARCH PAPER
1 Whitehead Institute for Biomedical Research, and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA; 2 Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA; 3 Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Dermatology, Harvard Medical School, Boston, Massachusetts 02115, USA
We have used nuclear transplantation to test whether the reprogramming activity of oocytes can reestablish developmental pluripotency of malignant cancer cells. We show here that the nuclei of leukemia, lymphoma, and breast cancer cells could support normal preimplantation development to the blastocyst stage but failed to produce embryonic stem (ES) cells. However, a blastocyst cloned from a RAS-inducible melanoma nucleus gave rise to ES cells with the potential to differentiate into multiple cell types in vivo including melanocytes, lymphocytes, and fibroblasts. Chimeras produced from these ES cells developed cancer with higher penetrance, shorter latency, and an expanded tumor spectrum when compared with the donor mouse model. These results demonstrate that the secondary changes of a melanoma nucleus are compatible with a broad developmental potential but predispose mice to melanomas and other malignant tumors on reactivation of RAS. Our findings serve as a paradigm for studying the tumorigenic effect of a given cancer genome in the context of a whole animal.
[Keywords: Cancer; epigenetics; nuclear transfer; reprogramming; pluripotency; embryonic stem cells]
Received April 21, 2004; revised version accepted June 2, 2004.
4 These authors contributed equally to this work.
5 E-MAIL Lynda_Chin{at}dfci.harvard.edu; FAX (617) 632-6069.
6 E-MAIL jaenisch{at}wi.mit.edu; FAX (617) 258-6505.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. P. Feinberg Epigenetics at the Epicenter of Modern Medicine JAMA, March 19, 2008; 299(11): 1345 - 1350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. K. Rajasekhar and M. Begemann Concise Review: Roles of Polycomb Group Proteins in Development and Disease: A Stem Cell Perspective Stem Cells, October 1, 2007; 25(10): 2498 - 2510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Williams Konrad Hochedlinger: The new kid of nuclear reprogramming J. Cell Biol., September 24, 2007; 178(7): 1098 - 1099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.L Green, D.N Wells, and B Oback Cattle Cloned from Increasingly Differentiated Muscle Cells Biol Reprod, September 1, 2007; 77(3): 395 - 406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K Berg, C. Li, G. Asher, D. N Wells, and B. Oback Red Deer Cloned from Antler Stem Cells and Their Differentiated Progeny Biol Reprod, September 1, 2007; 77(3): 384 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Gestl, T. L. Leonard, J. L. Biddle, M. T. Debies, and E. J. Gunther Dormant Wnt-Initiated Mammary Cancer Can Participate in Reconstituting Functional Mammary Glands Mol. Cell. Biol., January 1, 2007; 27(1): 195 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Blelloch, Z. Wang, A. Meissner, S. Pollard, A. Smith, and R. Jaenisch Reprogramming Efficiency Following Somatic Cell Nuclear Transfer Is Influenced by the Differentiation and Methylation State of the Donor Nucleus Stem Cells, September 1, 2006; 24(9): 2007 - 2013. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-M. Postovit, E. A. Seftor, R. E.B. Seftor, and M. J.C. Hendrix Influence of the Microenvironment on Melanoma Cell Fate Determination and Phenotype Cancer Res., August 15, 2006; 66(16): 7833 - 7836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Chin, L. A. Garraway, and D. E. Fisher Malignant melanoma: genetics and therapeutics in the genomic era. Genes & Dev., August 15, 2006; 20(16): 2149 - 2182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. J. Huijbers, P. Krimpenfort, P. Chomez, M. A. van der Valk, J.-Y. Song, E.-M. Inderberg-Suso, A.-M. Schmitt-Verhulst, A. Berns, and B. J. Van den Eynde An Inducible Mouse Model of Melanoma Expressing a Defined Tumor Antigen. Cancer Res., March 15, 2006; 66(6): 3278 - 3286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Kulesa, J. C. Kasemeier-Kulesa, J. M. Teddy, N. V. Margaryan, E. A. Seftor, R. E. B. Seftor, and M. J. C. Hendrix Reprogramming metastatic melanoma cells to assume a neural crest cell-like phenotype in an embryonic microenvironment PNAS, March 7, 2006; 103(10): 3752 - 3757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hong, A. Maunakea, P. Jun, A. W. Bollen, J. G. Hodgson, D. D. Goldenberg, W. A. Weiss, and J. F. Costello Shared Epigenetic Mechanisms in Human and Mouse Gliomas Inactivate Expression of the Growth Suppressor SLC5A8 Cancer Res., May 1, 2005; 65(9): 3617 - 3623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wakayama, H. Ohta, S. Kishigami, N. Van Thuan, T. Hikichi, E. Mizutani, M. Miyake, and T. Wakayama Establishment of Male and Female Nuclear Transfer Embryonic Stem Cell Lines from Different Mouse Strains and Tissues Biol Reprod, April 1, 2005; 72(4): 932 - 936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.J. BISSELL, P.A. KENNY, and D.C. RADISKY Microenvironmental Regulators of Tissue Structure and Function Also Regulate Tumor Induction and Progression: The Role of Extracellular Matrix and Its Degrading Enzymes Cold Spring Harb Symp Quant Biol, January 1, 2005; 70(0): 343 - 356. [Abstract] [PDF]
|
|
|
|
 |
|
 Of Mice and Melanoma Journal Watch Dermatology, November 9, 2004; 2004(1109): 3 - 3. [Full Text]
|
|
|
|
|
|
C. Brownlee Inaugural Article: Biography of Rudolf Jaenisch PNAS, September 28, 2004; 101(39): 13982 - 13984. [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. List, J. Vardiman, J.-P. J. Issa, and T. M. DeWitte Myelodysplastic Syndromes Hematology, January 1, 2004; 2004(1): 297 - 317. [Abstract] [Full Text] [PDF]
|
|
