Epigenetic activation of Gi-2 protein, the product of a putative protooncogene, mediates tumor promotion in vitro.
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Epigenetic activation of Gi-2 protein, the product of a putative protooncogene, mediates tumor promotion in vitro. / Harbers, M; Borowski, P; Fanick, Werner; Lengyel, H; Buck, F; Hinsch, K D; Hilz, H.
In: CARCINOGENESIS, Vol. 13, No. 12, 12, 1992, p. 2403-2406.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Epigenetic activation of Gi-2 protein, the product of a putative protooncogene, mediates tumor promotion in vitro.
AU - Harbers, M
AU - Borowski, P
AU - Fanick, Werner
AU - Lengyel, H
AU - Buck, F
AU - Hinsch, K D
AU - Hilz, H
PY - 1992
Y1 - 1992
N2 - Promotion of 'initiated' JB6 epidermal cells to the tumor phenotype can be effected by 12-O-tetradecanoylphorbol-13-acetate treatment, by stimulation of epidermal growth factor (EGF) receptor activity with EGF or transforming growth factor alpha and by exposure to the isoquinoline derivative H7. When these cells were incubated with pertussis toxin (PTX), induction of anchorage-independent growth by all four promoting substances was suppressed. The inhibition is specific since cell proliferation is not affected, suggesting that activation of a Gi protein is essential for promotion of the epidermal cells. This interpretation is strongly supported by the observation that the wasp poison mastoparan, which is known to mimic receptor-mediated activation of certain Gi proteins, also promoted anchorage independence. Immunological data and partial amino acid sequence analysis of ADP-ribosyl alpha i isolated from PTX-treated JB6 cells indicate that a Gi-2 protein is a mediator to tumor promotion in this system. The inhibitory action of 4-bromophenacyl bromide may point to a coupling of the Gi protein to phospholipase A2. From our data we infer that promoters induce the tumor phenotype in 'initiated' JB6 epidermal cells by activating epigenetically the same Gi protein that in a number of adrenal and ovarian tumors appears to be persistently activated by mutational events.
AB - Promotion of 'initiated' JB6 epidermal cells to the tumor phenotype can be effected by 12-O-tetradecanoylphorbol-13-acetate treatment, by stimulation of epidermal growth factor (EGF) receptor activity with EGF or transforming growth factor alpha and by exposure to the isoquinoline derivative H7. When these cells were incubated with pertussis toxin (PTX), induction of anchorage-independent growth by all four promoting substances was suppressed. The inhibition is specific since cell proliferation is not affected, suggesting that activation of a Gi protein is essential for promotion of the epidermal cells. This interpretation is strongly supported by the observation that the wasp poison mastoparan, which is known to mimic receptor-mediated activation of certain Gi proteins, also promoted anchorage independence. Immunological data and partial amino acid sequence analysis of ADP-ribosyl alpha i isolated from PTX-treated JB6 cells indicate that a Gi-2 protein is a mediator to tumor promotion in this system. The inhibitory action of 4-bromophenacyl bromide may point to a coupling of the Gi protein to phospholipase A2. From our data we infer that promoters induce the tumor phenotype in 'initiated' JB6 epidermal cells by activating epigenetically the same Gi protein that in a number of adrenal and ovarian tumors appears to be persistently activated by mutational events.
KW - Animals
KW - Female
KW - Cells, Cultured
KW - Mice
KW - Mutation
KW - Rats
KW - Phenotype
KW - Amino Acid Sequence
KW - Molecular Sequence Data
KW - Sequence Homology, Amino Acid
KW - Cell Transformation, Neoplastic/genetics
KW - Adrenal Gland Neoplasms/genetics
KW - Epidermal Growth Factor/pharmacology
KW - GTP-Binding Proteins/genetics/metabolism
KW - Ovarian Neoplasms/genetics
KW - Pertussis Toxin
KW - Phospholipases A/metabolism
KW - Phospholipases A2
KW - Proto-Oncogene Proteins/genetics/metabolism
KW - Tetradecanoylphorbol Acetate
KW - Transforming Growth Factor alpha/pharmacology
KW - Virulence Factors, Bordetella/pharmacology
KW - Animals
KW - Female
KW - Cells, Cultured
KW - Mice
KW - Mutation
KW - Rats
KW - Phenotype
KW - Amino Acid Sequence
KW - Molecular Sequence Data
KW - Sequence Homology, Amino Acid
KW - Cell Transformation, Neoplastic/genetics
KW - Adrenal Gland Neoplasms/genetics
KW - Epidermal Growth Factor/pharmacology
KW - GTP-Binding Proteins/genetics/metabolism
KW - Ovarian Neoplasms/genetics
KW - Pertussis Toxin
KW - Phospholipases A/metabolism
KW - Phospholipases A2
KW - Proto-Oncogene Proteins/genetics/metabolism
KW - Tetradecanoylphorbol Acetate
KW - Transforming Growth Factor alpha/pharmacology
KW - Virulence Factors, Bordetella/pharmacology
M3 - SCORING: Journal article
VL - 13
SP - 2403
EP - 2406
JO - CARCINOGENESIS
JF - CARCINOGENESIS
SN - 0143-3334
IS - 12
M1 - 12
ER -
