Notch, Myc and breast cancer.
The involvement of Myc in the development of human breast cancer is known for quite some time, but an analogous role of Notch signaling is only now emerging from fragmented pieces of information. Recently, a Notch/Myc relationship in oncogenesis was revealed from a mouse model, in which mammary tumors are induced by the intracellular domain of Notch1 (N1(IC)). In fact, a combination of genetic and molecular data demonstrated that Myc is a direct transcriptional target of Notch1 participating as an indispensable downstream effector in N1(IC)-induced tumorigenic action. A medically-relevant correlative observation based on immunophenotyping was the coexpression of Notch1 and Myc in a significant fraction of human breast cancer specimens. A Notch1/Myc oncogenic association was also observed in T-cell acute lymphoblastic leukemia.
Efstratiadis
Argiris
A
Department of Genetics and Development, Columbia University Medical Center, New York, New York 10032, USA. ae4@columbia.edu
Szabolcs
Matthias
M
Klinakis
Apostolos
A
D000818:Animals; D030801:Animals, Genetically Modified / Q000378:metabolism; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics; D008321:Mammary Glands, Animal / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D010802:Phylogeny; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C489427:MYC protein, human; C497761:NOTCH1 protein, human; D016271:Proto-Oncogene Proteins c-myc; D051881:Receptor, Notch1