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Transforming growth factor-beta (TGF beta) inhibits TGF alpha expression in bovine anterior pituitary-derived cells
1Department of Clinical Biochemistry, University of Toronto, Ontario, Canada.
Abstract:
Transforming growth factor-beta 1 (TGF beta 1) is a multifunctional regulator of cell growth and differentiation. We report here that TGF beta 1 decreased the proliferation of nontransformed bovine anterior pituitary-derived cells grown in culture. We have previously demonstrated that these cells express both TGF alpha and its receptor [the epidermal growth factor (EGF) receptor] and that expression can be stimulated by phorbol ester (TPA) and EGF. TGF beta 1 treatment over a 2-day period decreased the proliferation of pituitary cells. This decreased growth rate was accompanied by a decrease in the TGF alpha mRNA level. The effect of TGF beta 1 on TGF alpha mRNA down-regulation was both dose dependent (maximal effect observed at 1.0 ng/ml TGF beta 1) and time dependent (minimum of 2-day treatment with TGF beta 1 was required before a decrease in TGF alpha mRNA was observed). Studies on TGF alpha mRNA stability indicated that TGF beta 1 did not alter the TGF alpha mRNA half-life. Treatment of the TGF beta 1 down-regulated cells with EGF resulted in the stimulation of TGF alpha mRNA levels; thus, the TGF beta 1-treated cells remained responsive to EGF. The decreased proliferation in response to TGF beta 1 could be only partially reversed by simultaneous treatment of the cells with EGF (10(-9)M) and TGF beta 1 (3.0 ng/ml). Qualitatively, the TGF beta 1-induced reduction of TGF alpha mRNA content was independent of cell density. TGF beta 1 treatment of the anterior pituitary-derived cells also reduced the levels of c-myc and EGF receptor mRNA. These results represent the first demonstration of the down-regulation of TGF alpha synthesis by a polypeptide growth factor and suggest that TGF beta 1 may be a physiological regulator of TGF alpha production in vivo.
Insights
Transforming growth factor-beta 1 (TGF beta 1) inhibits bovine pituitary cell proliferation and down-regulates TGF alpha mRNA. This study reveals TGF beta 1 as a potential physiological regulator of TGF alpha production.
Area of Science:
- Cell Biology
- Molecular Biology
- Endocrinology
Background:
- Transforming growth factor-beta 1 (TGF beta 1) is a key regulator of cell functions.
- Bovine anterior pituitary cells express TGF alpha and its receptor, the epidermal growth factor (EGF) receptor.
- Previous studies showed TPA and EGF can stimulate TGF alpha and EGF receptor expression.
Purpose of the Study:
- To investigate the effect of TGF beta 1 on the proliferation of bovine anterior pituitary cells.
- To determine if TGF beta 1 influences the expression of TGF alpha mRNA.
- To explore the role of TGF beta 1 in regulating TGF alpha synthesis.
Main Methods:
- Primary bovine anterior pituitary cells were cultured and treated with varying doses and durations of TGF beta 1.
- Cell proliferation was assessed.
- TGF alpha mRNA levels were quantified using molecular techniques.
- mRNA stability assays were performed.
- Cells were treated with EGF to assess responsiveness.
Main Results:
- TGF beta 1 significantly decreased pituitary cell proliferation in a dose- and time-dependent manner.
- TGF beta 1 treatment led to a reduction in TGF alpha mRNA levels.
- TGF beta 1 did not affect TGF alpha mRNA stability but reduced its overall content.
- Cells remained responsive to EGF, which could stimulate TGF alpha mRNA levels.
- TGF beta 1 also reduced c-myc and EGF receptor mRNA levels.
- The inhibitory effect of TGF beta 1 on proliferation was only partially reversed by EGF.
Conclusions:
- TGF beta 1 down-regulates TGF alpha mRNA levels in bovine anterior pituitary cells.
- TGF beta 1 inhibits cell proliferation and reduces TGF alpha, c-myc, and EGF receptor mRNA.
- These findings suggest TGF beta 1 may act as a physiological regulator of TGF alpha production in vivo.