Post-transcriptional control regulates transforming growth factor α in the human carcinoma KB cell line

Gabriella Nicolini, Mariarosaria Miloso, Maria Cristina Moroni, Laura Beguinot, Luigi Scotto

Research output: Contribution to journalArticle

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Abstract

Expression of epidermal growth factor receptor (EGF-R) antisense RNA results in a drastic reduction of EGF-R levels in the human carcinoma KB cell line and induces a reversion of their transformed phenotype (Moroni, M. C., Willingham, M. C., and Beguinot, L. (1992) J. Biol. Chem. 267, 2714-2722). We used parental and EGF-R antisense KB clones as a genetic system to study, in the same cell line, the role of transforming growth factor α (TGF-α) in the establishment and maintenance of the transformed phenotype. KB cells produce TGF-α mRNA, and their conditioned medium is able to sustain growth of antisense cells, mimicking the effect of exogenous EGF or TGF-α. In antisense cells there is a marked reduction of TGF-α mRNA steady-state levels. In addition, the decrease in TGF-α parallels the levels of residual EGF-R in the various antisense clones, indicating a direct correlation between receptors and growth factor levels. The addition of exogenous TGF-α (10 ng/ml) to antisense clones induces TGF-α levels. The half-life of TGF- α mRNA is 40-60 min in antisense cells and more than 8 h in parental KB cells, as determined by actinomycin D decay curves. This result indicates a predominant regulation of TGF-α mRNA at the post-transcriptional level. Nuclear run-on experiments show that there is only a marginal effect at the transcriptional level. We conclude that the autocrine loop responsible for the transformed phenotype of the human carcinoma KB cell line is dependent on both elevated levels of EGF-R and the presence of TGF-α. In addition, TGF- α is able to induce its own mRNA via a signal due to activation of the EGF- R acting predominantly at the post-transcriptional level.

Original languageEnglish
Pages (from-to)30290-30296
Number of pages7
JournalJournal of Biological Chemistry
Volume271
Issue number47
DOIs
Publication statusPublished - 1996

Fingerprint

KB Cells
Transforming Growth Factors
Cells
Carcinoma
Cell Line
Epidermal Growth Factor Receptor
Messenger RNA
Clone Cells
Phenotype
Epidermal Growth Factor
Antisense RNA
Growth Factor Receptors
Dactinomycin
Conditioned Culture Medium
Half-Life
Chemical activation
Maintenance

ASJC Scopus subject areas

  • Biochemistry

Cite this

Post-transcriptional control regulates transforming growth factor α in the human carcinoma KB cell line. / Nicolini, Gabriella; Miloso, Mariarosaria; Moroni, Maria Cristina; Beguinot, Laura; Scotto, Luigi.

In: Journal of Biological Chemistry, Vol. 271, No. 47, 1996, p. 30290-30296.

Research output: Contribution to journalArticle

Nicolini, Gabriella ; Miloso, Mariarosaria ; Moroni, Maria Cristina ; Beguinot, Laura ; Scotto, Luigi. / Post-transcriptional control regulates transforming growth factor α in the human carcinoma KB cell line. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 47. pp. 30290-30296.
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