c-Myc expression is controlled by the mitogenic cAMP-cascade in thyrocytes

Area of Science:

• Molecular Endocrinology
• Cellular Signaling
• Oncogene Regulation

Background:

• Thyroid epithelial cells respond to thyrotropin (TSH) with proliferation and differentiation via cAMP.
• Epidermal growth factor (EGF) and phorbol esters promote proliferation and dedifferentiation.
• The c-myc protooncogene plays a critical role in cell growth and differentiation.

Purpose of the Study:

• To elucidate the regulation of c-myc protooncogene mRNA and protein expression by cAMP in dog thyroid epithelial cells.
• To investigate the mechanisms underlying the biphasic regulation of c-myc by the cAMP signaling pathway.

Main Methods:

• Primary culture of dog thyroid epithelial cells.
• Measurement of c-myc mRNA and protein levels following TSH stimulation.
• In vitro transcriptional elongation assays to assess transcription rates.
• Actinomycin D chase experiments to determine mRNA stability.

Main Results:

• TSH-induced cAMP signaling resulted in a biphasic increase in c-myc mRNA and protein.
• The initial phase involved cAMP-mediated release of a transcriptional elongation block, not initiation.
• c-myc mRNA stability was enhanced by TSH treatment during the first phase, but this effect diminished later.
• Transcription was subsequently shut off in the second phase, with loss of mRNA stabilization.

Conclusions:

• cAMP signaling regulates c-myc expression in a biphasic manner in thyroid epithelial cells.
• This regulation occurs through combined transcriptional (elongation block release) and post-transcriptional (mRNA stabilization) mechanisms.
• The findings highlight complex control of protooncogene expression in response to hormonal stimulation driving cell proliferation and differentiation.