Autocrine transforming growth factor-β1 and β2 expression is increased by cell crowding and quiescence in colon carcinoma cells

Luzhe Sun, W. U. Shaoping, Kevin Coleman, Karla C. Fields, Lisa E. Humphrey, Michael G. Brattain

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Although a great deal is known about the cellular effects of exogenous transforming growth factor-β (TGFβ) treatment and the effects of various exogenous agents (including TGF-β's themselves) on TGF-β expression, studies of cellular controls for autocrine TGF-β expression and function have been rare. Since exogenous TGF-β treatment blocks progression through the cell cycle, it seemed likely that autocrine TGF-β activity would be induced by growth states in which there was little or no cell division such as confluency or quiescence. Specific TGF-β1 or β2 neutralizing antibody treatment of a colon carcinoma cell line designated CBS showed that autocrine TGF-β activity could be demonstrated in quiescent cells but not in preconfluent cells. Studies of kinetics of TGF-β1 and β2 mRNA levels during the establishment of quiescence revealed a significant increase of both isoforms in quiescent cells. The quiescent cells also secreted three- to fourfold and four to fivefold higher levels of total (latent plus active) TGF-β1 and β2 protein in the conditioned media than the confluent cells and preconfluent cells, respectively. There was no detectable active form of either TGF-β isoform in the conditioned media of preconfluent cells, whereas a significant amount of active TGF-β1 and β2 was detected in the conditioned media of quiescent cells. Quantitative RNase protection assays were developed to compare the effects of cell crowding vs quiescence on TGF-β expression. TGF-β1 was primarily induced by quiescence. TGF-β2 was induced by both quiescence and cell crowding. Increased TGF-β1 mRNA levels appeared to be exclusively due to an increase in stability, while increased TGF-β2 mRNA levels were due to increased transcription. This growth state-related induction of TGF-β's was also observed in two other colon carcinoma cell lines. These studies show that TGF-β1 and β2 are autocrine-negative factors which can be situationally expressed by cells as a function of their growth state. Autocrine expression of the TGF-β's in this model system appears not to affect exponentially growing cells, but rather to function by maintaining a quiescent state and/or by blocking progression through the cell cycle.

Original languageEnglish (US)
Pages (from-to)215-224
Number of pages10
JournalExperimental Cell Research
Volume214
Issue number1
DOIs
StatePublished - Sep 1994

ASJC Scopus subject areas

  • Cell Biology

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