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Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia

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Ets1 induces dysplastic changes when expressed in terminally-differentiating squamous epidermal cells.

Priyadharsini Nagarajan¹, Neha Parikh, Lee Ann Garrett-Sinha

¹Department of Biochemistry, State University of New York at Buffalo, Center for Excellence in Bioinformatics and Life Sciences, Buffalo, New York, USA.

|January 15, 2009

Summary

The Ets1 oncogene drives early pre-neoplastic changes in squamous cell cancers by promoting proliferation and blocking differentiation. Upregulation of Ets1 is crucial for both early and late stages of tumor development, including invasion.

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Area of Science:

Oncology
Molecular Biology
Dermatology

Background:

Ets1 is an oncogene and transcription factor regulating genes in tumor initiation and progression.
Ets1 overexpression correlates with invasion and metastasis in squamous cell cancers.
Ets1's role in early oncogenesis was previously underestimated.

Purpose of the Study:

To investigate the role of Ets1 in squamous cell carcinogenesis.
To define the temporal and spatial regulation of Ets1 in epithelial tissues.

Main Methods:

Generated a transgenic mouse model with inducible Ets1 expression.
Analyzed epithelial organization, proliferation, and differentiation upon Ets1 induction.
Identified Ets1 transcriptional targets in vivo.

Main Results:

Ets1 induction caused increased proliferation and blocked differentiation in stratified squamous epithelium.
Phenotypic changes were reversible upon Ets1 suppression.
Re-induced Ets1 led to localized, invasive lesions.
Upregulated MMP13 was identified as a direct Ets1 transcriptional target.

Conclusions:

Ets1 upregulation can be an early event promoting pre-neoplastic changes.
Ets1 regulates key genes involved in epidermal growth and invasion.
Ets1 oncogene is significant in both early and late stages of tumor development.