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Updated: Jun 22, 2026
08:35
Inducible and Reversible Dominant-negative (DN) Protein Inhibition
Published on: January 7, 2019
Transcript level modulates the inherent oncogenicity of RET/PTC oncoproteins
Douglas S Richardson1, Taranjit S Gujral, Susan Peng
1Department of Pathology and Molecular Medicine, Division of Cancer Biology and Genetics, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.
Cancer Research
|June 3, 2009
Summary
RET proto-oncogene rearrangements drive thyroid cancer. While RET/PTC oncoproteins are highly oncogenic, their lower expression in papillary thyroid cancer (PTC) explains its indolent nature compared to medullary thyroid cancer (MTC).
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- RET proto-oncogene mutations are prevalent in thyroid cancer, affecting both medullary (MTC) and papillary (PTC) forms.
- RET fusion oncogenes in PTC are key examples of chimeric oncoproteins in solid tumors.
- The differing clinical behavior between RET-related MTC and PTC remains poorly understood.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms underlying the distinct oncogenicity of RET/PTC rearrangements in thyroid cancer.
- To characterize the two most common RET/PTC rearrangements, PTC1 and PTC3.
Main Methods:
- Cellular and molecular characterization of RET/PTC rearrangements (PTC1 and PTC3).
- Analysis of RET/PTC oncoprotein oncogenicity, cell proliferation, and transformation.
- Assessment of downstream signaling pathways activated by RET/PTCs.
- Quantification of transcript levels for RET, CCDC6, and NCOA4 in PTCs and MTCs.
Main Results:
- Overexpressed RET/PTC oncoproteins are highly oncogenic, promoting cell proliferation and transformation.
- RET/PTCs activate similar downstream signaling cascades as wild-type RET, but at varying levels.
- RET/PTCs exhibit increased stability due to resistance to lysosomal degradation.
- Transcript levels of RET, CCDC6, and NCOA4 are lower in PTCs compared to MTCs.
Conclusions:
- RET/PTC oncoproteins (PTC1 and PTC3) are potent oncogenes when overexpressed.
- The relatively low expression driven by NCOA4 and CCDC6 promoters in vivo contributes to the indolent phenotype of RET-associated PTC compared to MTC.
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