Related Experiment Video
Updated: Jun 27, 2026
Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia
Published on: July 25, 2017
Differential regulation of Dlg1, Scrib, and Lgl1 expression in a transgenic mouse model of ocular cancer
V Vieira1, G de la Houssaye, E Lacassagne
1Université Paris-Descartes, CERTO, Centre de Recherches Thérapeutiques en Ophtalmologie de Faculté de Médecine Paris- Descartes-site Necker, EA no2502 du Ministère de Recherche, AP-HP, Paris, France.
Purpose:
Discs large (dlg), scribble (scrib), and lethal giant larvae (lgl) are major suppressor genes in Drosophila melanogaster. They encode proteins that regulate cell polarity and cell proliferation in Drosophila and mammals. However, their basic oncogenic roles have not yet been established in mouse epithelial ocular cancer. We evaluated the potential implication of these proteins in tumorigenesis of adenocarcinomas originating from the retinal pigmented epithelium of the Trp1/Tag transgenic mouse model. We examined the changes in the distribution and levels of these proteins in mouse ocular tissues from the Trp1/Tag mouse model.
Methods:
The expression patterns of theses genes and their corresponding proteins in normal mouse ocular tissues were studied by in situ hibridization and immunohistofluorescence experiments. In addition, variations in mRNA and proteins levels and protein distributions for Dlg1, Scrib, and Lgl1 were analyzed in the ocular tissues from Trp1/Tag transgenic mouse model by reverse transcription polymerase chain reaction (RT-PCR), western blot analysis, and immunohistofluorescence.
Results:
We found that mouse Dlg1, Scrib, and Lgl1 are widely distributed in normal ocular tissues, particularly in retinal neurons. We found that the three proteins are mislocalized in retinal layers during ocular carcinogenesis. These mislocalizations were correlated to the early dysplastic stages of ocular tumorigenesis. Additionally, the mislocalization of each protein was associated with its downregulation. Decreased levels of these proteins may be considered as late-stage markers of the disease but also as markers of the invasive stage of this cancerous process. This downregulation may be involved in epithelial-mesenchymal transition in this mouse ocular tumoral model. This would be consistent with the downregulation of E-cadherin and upregulation of N-cadherin expression observed in this model.
Conclusions:
This is the first study to demonstrate the involvement of Dlg1, Scrib, and Lgl1 in a mouse with ocular adenocarcinoma and the simultaneous involvement of these proteins in the same cancer. Our results indicate that both the mislocalization and downregulation of these proteins may be involved together in ocular carcinogenesis.
Insights
Discs large (Dlg1), Scribble (Scrib), and Lethal giant larvae (Lgl1) proteins are crucial for cell regulation. Their mislocalization and downregulation in mouse ocular tissues indicate a role in ocular adenocarcinoma development and progression.
Area of Science:
- Ocular oncology
- Molecular biology
- Cancer genetics
Background:
- Discs large (Dlg1), Scribble (Scrib), and Lethal giant larvae (Lgl1) are key tumor suppressor genes regulating cell polarity and proliferation in model organisms.
- Their specific roles in the initiation and progression of mouse ocular cancer remain largely uncharacterized.
Purpose of the Study:
- To investigate the involvement of Dlg1, Scrib, and Lgl1 proteins in ocular tumorigenesis.
- To analyze alterations in their distribution and expression levels in a mouse model of retinal pigmented epithelium adenocarcinoma.
Main Methods:
- In situ hybridization and immunohistofluorescence for expression patterns in normal ocular tissues.
- RT-PCR, western blot, and immunohistofluorescence to analyze changes in mRNA, protein levels, and distribution in the Trp1/Tag mouse model.
Main Results:
- Dlg1, Scrib, and Lgl1 proteins are widely distributed in normal mouse ocular tissues, especially retinal neurons.
- These proteins exhibit mislocalization in retinal layers during ocular carcinogenesis, correlating with early dysplastic stages.
- Mislocalization is associated with protein downregulation, potentially marking late-stage or invasive cancer and contributing to epithelial-mesenchymal transition.
Conclusions:
- This study is the first to report the involvement of Dlg1, Scrib, and Lgl1 in mouse ocular adenocarcinoma.
- Both mislocalization and downregulation of these proteins appear to play a simultaneous role in ocular carcinogenesis.
More Related Videos
10:31The Drosophila Imaginal Disc Tumor Model: Visualization and Quantification of Gene Expression and Tumor Invasiveness Using Genetic Mosaics
Published on: October 6, 2016
13:47Laser Capture Microdissection of Highly Pure Trabecular Meshwork from Mouse Eyes for Gene Expression Analysis
Published on: June 3, 2018
