TY - JOUR
T1 - 5-azacytidine-lnduced uncoupling of differentiation and tumorigenicity in a murine cell line
AU - Walker, C.
AU - Ranney, D. F.
AU - Shay, J. W.
N1 - Funding Information:
I Received November 7, 1983; accepted May 22, 1984. 2 Supported in part by grants from the National Science Foundation (PCM-8023070) to J. W. S. and from the Eli Lilly & Co. to D. F. R. J Department of Cell Biology, The University of Texas Health Science Center at Dallas, 5323 Harry Hines Blvd., Dallas, Tex. 75235. 4 Present address: Laboratory of Pulmonary Function and Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, N.C. 27709. 5 Department of Pathology, The University of Texas Health Science Center at Dallas. 6 Address reprint requests to Dr. Shay. 7 We thank Dr. P. A. Jones for helpful discussions and Ms. B. Beck, Ms. D. Contreras, and Mrs. E. Johnson for technical assistance.
PY - 1984/1/1
Y1 - 1984/1/1
N2 - Highly tumorigenic, myogenically defective T984-15 murine cells were treated with the hypomethylating agent 5-azacytidine (5-azaC). In response to drug treatment, T984-15 cells formed colonies that were myosin-positive and contained fused myotubes. When cloned, these differentiated colonies gave rise to cells that maintained their myogenic potential even after prolonged growth in tissue culture. The myogenic differentiation observed in response to 5-azaC treatment was not the result of selection of a preexisting myogenic subpopulation, inasmuch as treatment of a subcloned population of nondifferentiating cells with 5-azaC also resulted in the induction of myogenesis. In addition to inducing myogenic potential, 5-azaC generally suppressed the tumorigenic potential of the treated cells. Whereas 19 of 19 untreated T984-15 clones when injected into BALB/c nude mice produced tumors, 8 of 9 of the 5-azaC-treated clones injected displayed suppressed tumorigenicity under identical conditions. Tumorigenic suppression, however, was independent of the induction of differentiation: 1 myogenic clone remained tumorigenic and 5 clones whose tumorigenic potential was suppressed were non myogenic. Thus treatment with the hypomethylating agent 5-azaC not only affected the expression of differentiated and tumorigenic phenotypes but also dissociated their usually coordinate regulation.
AB - Highly tumorigenic, myogenically defective T984-15 murine cells were treated with the hypomethylating agent 5-azacytidine (5-azaC). In response to drug treatment, T984-15 cells formed colonies that were myosin-positive and contained fused myotubes. When cloned, these differentiated colonies gave rise to cells that maintained their myogenic potential even after prolonged growth in tissue culture. The myogenic differentiation observed in response to 5-azaC treatment was not the result of selection of a preexisting myogenic subpopulation, inasmuch as treatment of a subcloned population of nondifferentiating cells with 5-azaC also resulted in the induction of myogenesis. In addition to inducing myogenic potential, 5-azaC generally suppressed the tumorigenic potential of the treated cells. Whereas 19 of 19 untreated T984-15 clones when injected into BALB/c nude mice produced tumors, 8 of 9 of the 5-azaC-treated clones injected displayed suppressed tumorigenicity under identical conditions. Tumorigenic suppression, however, was independent of the induction of differentiation: 1 myogenic clone remained tumorigenic and 5 clones whose tumorigenic potential was suppressed were non myogenic. Thus treatment with the hypomethylating agent 5-azaC not only affected the expression of differentiated and tumorigenic phenotypes but also dissociated their usually coordinate regulation.
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U2 - 10.1093/jnci/73.4.877
DO - 10.1093/jnci/73.4.877
M3 - Article
C2 - 6207331
AN - SCOPUS:0021146283
SN - 0027-8874
VL - 73
SP - 877
EP - 885
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 4
ER -