Mechanism of induction of c-fos by ultraviolet B (290-320 nm) in mouse JB6 epidermal cells

• Published in: Cancer research (Chicago, Ill.) Vol. 53; no. 1; pp. 38 - 45
• Main Authors: GIRISH SHAH, GHOSH, R, AMSTAD, P. A, CERUTTI, P. A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 1993
• Subjects: Animals; Base Sequence; Benzamides - pharmacology; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Cell Nucleus - chemistry; Cell Nucleus - metabolism; Cells, Cultured; DNA Damage; Down-Regulation - radiation effects; Epidermis - cytology; Epidermis - physiology; Epidermis - radiation effects; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - radiation effects; Genes, fos - physiology; Genes, fos - radiation effects; Male; Medical sciences; Mice; Molecular Sequence Data; Oligonucleotides - metabolism; Oncogene Protein p65(gag-jun) - genetics; Oncogene Protein p65(gag-jun) - metabolism; Oncogene Proteins v-fos - genetics; Oncogene Proteins v-fos - metabolism; Physical agents; Poly Adenosine Diphosphate Ribose - metabolism; Poly(ADP-ribose) Polymerase Inhibitors; Skin Neoplasms - etiology; Skin Neoplasms - genetics; Transcription, Genetic - radiation effects; Tumors; Ultraviolet Rays - adverse effects; Cell proliferation; Skin disease; UVB radiation; Toxicity; Rodentia; Activation; Malignant tumor; Carcinogenesis; Carcinogen; Vertebrata; Mammalia; Mouse; Animal; C-Onc gene; Skin; Mechanism of action; Protooncogene
• ISSN: 0008-5472; 1538-7445

The UVB (290-320 nm) portion of the solar spectrum possesses the highest activity for the induction of skin cancer and has the capacity to stimulate epidermal proliferation. We report that UVB is a transcriptional inducer of the c-fos protooncogene in mouse JB6 epidermal cells. Induction is biphasic with an immediate early peak at 30-60 min and a second broader peak 8 h following irradiation. The immediate early phase is suppressed by inhibitors of nuclear adenosine diphosphoribose transferase. For UVB induction, the formation of full-length messages is less efficient than of early, short messages, while both types of messages are produced at similar rates following serum stimulation. Experiments with stable transfectants with reporter constructs linked to 5'-upstream sequences of c-fos indicate that UVB and serum stimulation both require the sequences from -345 to -285 which contain the joint DSE-AP-1 enhancer motifs for efficient induction. Mobility shift data reveal that the complement of c-Fos and c-Jun proteins which bind to the fos-AP-1 octanucleotide decrease immediately following irradiation. Increased binding of Fos and Jun is observed 8-24 h later. UVB did not cause an observable change in the nuclear proteins which bind to the dyad symmetry element oligonucleotide in vitro. Fos protein was detected among the binding proteins. We propose that the two phases of UVB-induced c-fos expression occur by quite different mechanisms. The immediate early phase is inhibited by adenosine diphosphoribose transferase inhibitors because poly-ADP ribosylation of chromosomal proteins is required for the resealing of UVB-induced DNA strand breaks which otherwise retard message elongation. The production of an autocrine factor may be responsible for the late phase of c-fos induction.