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Updated: Jul 20, 2026
08:18
Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene
Published on: December 31, 2014
HMG-I/Y, a new c-Myc target gene and potential oncogene
L J Wood1, M Mukherjee, C E Dolde
1Hematology Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Molecular and Cellular Biology
|July 13, 2000
Summary
High-mobility group I/Y (HMG-I/Y) proteins are key in cell growth and cancer. This study reveals HMG-I/Y is a direct target of c-Myc, driving neoplastic transformation and acting as a potential oncogene.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- High-mobility group I/Y (HMG-I/Y) proteins are architectural chromatin binders crucial for gene transcription.
- Increased HMG-I/Y expression correlates with cellular proliferation, neoplastic transformation, and human cancers, but its precise role in malignancy is unclear.
Purpose of the Study:
- To investigate the regulation and function of HMG-I/Y proteins in cell growth and transformation.
- To elucidate the relationship between HMG-I/Y and the oncoprotein c-Myc in the context of cancer development.
Main Methods:
- Cloning, sequencing, and mutagenesis of the HMG-I/Y promoter.
- In vitro DNA binding assays and transfection experiments to assess protein interactions and transcriptional activation.
- Analysis of HMG-I/Y expression in various cell lines, including Myc-deficient fibroblasts and Burkitt's lymphoma cells.
- Assessment of neoplastic transformation and tumor formation in response to altered HMG-I/Y expression, including the use of antisense constructs.
Main Results:
- A c-Myc-Max binding site was identified as critical for serum stimulation of the HMG-I/Y promoter.
- c-Myc directly binds to this site and activates HMG-I/Y transcription, establishing HMG-I/Y as a direct c-Myc target gene.
- HMG-I/Y expression is elevated in Burkitt's lymphoma cells with high c-Myc levels.
- Overexpression of HMG-I induces neoplastic transformation and tumor formation in rodent cell lines and abrogates transformation in lymphoma cells when expression is reduced.
Conclusions:
- HMG-I/Y is a direct transcriptional target of c-Myc.
- HMG-I/Y plays a significant role in neoplastic transformation.
- HMG-I/Y represents a new class of potential oncogenes involved in cancer pathogenesis.
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