Lack of sustained regression of c-MYC-induced mammary adenocarcinomas following brief or prolonged MYC inactivation.
Recent studies of oncogene dependence in conditional transgenic mice have suggested the exciting possibility that transient or prolonged MYC inactivation may be sufficient for sustained reversal of the tumorigenic process. In contrast, we report here that following oncogene downregulation, the majority of c-MYC-induced mammary adenocarcinomas grow in the absence of MYC overexpression. In addition, residual neoplastic cells persist from virtually all tumors that do regress to a nonpalpable state and these residual cells rapidly recover their malignant properties following MYC reactivation or spontaneously recur in a MYC-independent manner. Thus, MYC-induced mammary tumor cells subjected to either brief or prolonged MYC inactivation remain exquisitely sensitive to its oncogenic effects and characteristically progress to a state in which growth is MYC-independent.
Boxer
Robert B
RB
Department of Cancer Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Jang
Joanne W
JW
Sintasath
Louis
L
Chodosh
Lewis A
LA
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D020287:In Situ Nick-End Labeling; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000502:physiology; D016283:Proto-Oncogene Proteins p21(ras); D012008:Recurrence; D012074:Remission Induction; D013997:Time Factors; D018631:ras Proteins / Q000235:genetics
D016271:Proto-Oncogene Proteins c-myc; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins