Transcription factor profiling shows new ways towards new treatment options of cutaneous T cell lymphomas.
Most oncogenes encode activators of transcription factors or transcription factors themselves. Transcription factors that are induced by growth stimuli are, in contrast to transcription factors that regulate house keeping genes, tightly regulated and only active, when a stimulus (e.g. cytokines or other growth factors) is given. Examples of such transcription factors are members of the jun, fos, myc, NFkB and STAT gene families. In cancer cells this regulation is interrupted, resulting in constitutive activities of transcription factors that are normally silent. This in turn results in the increased expression of target genes that are necessary for growth and protection from apoptosis. Since inducible transcription factors are activated by specific pathways, the identification of unusual constitutively active transcription factors also identifies the involved signal transduction pathway. Inhibitors of the components of these pathways may be effective anti-cancer agents, as they interrupt the abnormal signalling and in cancer cells. We applied this strategy for two forms of cutaneous T cell lymphomas and identified several groups of agents that may be the prototypes of new drugs to fight these diseases.
Döbbeling
Udo
U
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. Udo.Doebbeling@usz.ch
D017209:Apoptosis; D020869:Gene Expression Profiling; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism* / Q000628:therapy; D009182:Mycosis Fungoides / Q000378:metabolism / Q000628:therapy; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism; D012751:Sezary Syndrome / Q000378:metabolism / Q000628:therapy; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism* / Q000628:therapy; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D050791:STAT Transcription Factors; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases