Turning cell cycle controller genes into cancer drugs. A role for an antiproliferative cytokine (betaGBP).
Cancer therapies based on drugs designed to interfere with specific targets within the molecular circuitry of cancer cells are currently under intense experimentation. Our strategy is based on the use of a naturally occurring immunomolecule which can selectively kill cancer cells, based on its ability to exploit genetic differences between normal and cancer cells. The betaGBP cytokine has previously been shown to negatively regulate the cell cycle by blocking cells in late S phase. In tumour cells, but not in normal cells, the S phase block has been shown to be followed by apoptosis. Mechanisms involved in S phase arrest have been pinpointed to downregulation of signalling and altered expression of cell cycle controller proteins, including E2F1, a transcription factor with ability to play a part in apoptosis. Here we discuss the use of betaGBP within the context of cancer surveillance and cancer therapeutics focussing on E2F1 as one mechanistic aspect relevant to betaGBP's selective induction of programmed cell death in cancer.
Mallucci
Livio
L
School of Health and Life Sciences, Cell Signalling and Growth Laboratory, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NN, UK. livio.mallucci@kcl.ac.uk
Wells
Valerie
V
Danikas
Antonios
A
Davies
Derek
D
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001943:Breast Neoplasms / Q000473:pathology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D037161:Galectins / Q000494:pharmacology*; D018816:Genes, cdc / Q000502:physiology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000473:pathology; D014157:Transcription Factors / Q000502:physiology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D037161:Galectins; D014157:Transcription Factors