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Estrogen-induced post-transcriptional modulation of c-myc proto-oncogene expression in human breast cancer cells

Santos, G F ; Scott, G K ; Lee, W M ; Liu, E ; Benz, C

The Journal of biological chemistry, 1988-07, Vol.263 (20), p.9565-9568 [Periódico revisado por pares]

Bethesda, MD: Elsevier Inc

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Título:
Estrogen-induced post-transcriptional modulation of c-myc proto-oncogene expression in human breast cancer cells
Autor: Santos, G F ; Scott, G K ; Lee, W M ; Liu, E ; Benz, C
Assuntos: Biological and medical sciences ; Breast Neoplasms - genetics ; Cycloheximide - pharmacology ; Estradiol - pharmacology ; Exons ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation - drug effects ; Humans ; Introns ; Molecular and cellular biology ; Molecular genetics ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins c-myc ; Receptors, Estrogen - metabolism ; RNA, Messenger - metabolism ; Tamoxifen - pharmacology ; Transcription, Genetic - drug effects ; Transcription. Transcription factor. Splicing. Rna processing ; Transfection ; Tumor Cells, Cultured
É parte de: The Journal of biological chemistry, 1988-07, Vol.263 (20), p.9565-9568
Descrição: The effects of estradiol (E2) on c-myc proto-oncogene expression were studied in the estrogen receptor (ER)-positive human breast cancer cell line, MCF-7. A biphasic modulation in c-myc mRNA levels occurs during the first 24 h of E2 (1 nM) exposure and in the absence of changes in MCF-7 culture growth, with transcript levels rising 4-6-fold within 1 h, returning to near base-line level after 3-6 h, and increasing again after 24 h of exposure. In contrast, the growth-inhibiting antiestrogen, tamoxifen (1 microM), reduces c-myc to 20% of the pretreatment level within 3-6 h of exposure, and this early decline is followed by a gradual return toward base-line level after continuous 72-h treatment. In ER-negative cells there is no change in c-myc expression following E2 exposure. MCF-7 nuclear runon assays show that c-myc transcription rates remain unchanged from base line for 24 h after E2 administration; as well, cycloheximide inhibition of protein synthesis superinduces c-myc expression and prevents E2 modulation of transcript levels. These results indicate that post-transcriptional modulation of c-myc by E2 is mediated by a labile degradative protein or otherwise dependent on active protein synthesis. We also developed MCF/nm and MCF/dm sublines by transfecting normal cells with human c-myc exons 2-3, transcriptionally driven by a retroviral long terminal repeat. Expression of the transfected c-myc genes in these sublines remains constant and elevated 10-fold, while transcript levels from the endogenous proto-oncogene continue to be modulated by E2. These findings suggest that in ER-positive breast cancer cells, E2 can modulate c-myc mRNA levels by a post-transcriptional mechanism that depends on gene sequences upstream from c-myc exon 2.
Editor: Bethesda, MD: Elsevier Inc
Idioma: Inglês

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Estrogen-induced post-transcriptional modulation of c-myc proto-oncogene expression in human breast cancer cells

Santos, G F ; Scott, G K ; Lee, W M ; Liu, E ; Benz, C

Bethesda, MD: Elsevier Inc

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