# FGFR2 and NOTCH1 Expression Inversely Correlated in Progressive Cutaneous Carcinogenesis in an Experimental Mouse Model

**Authors:** Georgia Vairaktari, Alexander Schramm, Efstathia Vairaktari, Spyridoula Derka, Andreas Sakkas, Nikolaos Lefantzis, Stavroula Diamantopoulou, Antonis Vylliotis, Andreas Lazaris, Marcel Ebeling, Stavros Vassiliou

PMC · DOI: 10.3390/jpm14070729 · Journal of Personalized Medicine · 2024-07-05

## TL;DR

This study shows that FGFR2 and NOTCH1 genes have opposite roles in skin cancer progression in mice, with FGFR2 linked to tumor development and NOTCH1 to early benign tumors.

## Contribution

The study reveals an inverse correlation between FGFR2 and NOTCH1 expression during skin cancer progression in an experimental mouse model.

## Key findings

- FGFR2 expression increases in benign, precancerous, and malignant tumors compared to normal tissue.
- NOTCH1 expression is elevated only in benign tumors compared to normal tissue.
- FGFR2 is correlated with tumor progression, while NOTCH1 is inversely correlated in FVB/N mice.

## Abstract

Cutaneous squamous cell carcinoma (cSCC) is a common and increasingly prevalent form of skin cancer, posing significant health challenges. Understanding the molecular mechanisms involved in cSCC progression is crucial for developing effective treatments. The primary aim of this research was to evaluate the activation of NOTCH1 and FGFR2 oncogenes in inducing skin cancer in FVB/N mice through a stepwise chemical process. Forty female FVB/N mice, aged four weeks, were randomly divided into a control group (n = 8) and two experimental groups (group A: n = 16, group B: n = 16). This study involved subjecting the groups to a two-stage carcinogenesis procedure. This included an initial application of 97.4 nmol DMBA on shaved skin on their backs, followed by applications of 32.4 nmol TPA after thirteen weeks for group A and after twenty weeks for group B. The control group did not receive any treatment. Their skin conditions were monitored weekly to detect tumor development. After the experiment, the animals were euthanized for further tissue sampling. The examination of skin lesions in the experimental groups showed a correlation with tumor progression, ranging from dysplasia to carcinoma. Tumor samples were assessed both histologically and immunohistochemically. Notably, FGFR2 expression was higher in benign, precancerous, and malignant tumors compared to normal tissue. NOTCH1 expression was only elevated in benign tumors compared to normal tissue. This study demonstrates a clear correlation of FGFR2 expression and the progression of cutaneous neoplasms, while NOTCH 1 expression is inversely correlated in FVB/N mice. This suggests an early involvement of these oncogenes in the development of skin tumors.

## Linked entities

- **Genes:** FGFR2 (fibroblast growth factor receptor 2) [NCBI Gene 2263], NOTCH1 (notch receptor 1) [NCBI Gene 4851]
- **Chemicals:** DMBA (PubChem CID 6001), TPA (PubChem CID 88055650)
- **Diseases:** cutaneous squamous cell carcinoma (MONDO:0002529), skin cancer (MONDO:0002898)

## Full-text entities

- **Genes:** Fgfr2 (fibroblast growth factor receptor 2) [NCBI Gene 14183] {aka Bek, Fgfr-2, Fgfr-7, Fgfr2b, Fgfr7, KGFR}, Notch1 (notch 1) [NCBI Gene 18128] {aka 9930111A19Rik, Mis6, N1, Tan1, lin-12}
- **Diseases:** skin cancer (MESH:D012878), skin lesions (MESH:D012871), precancerous (MESH:D011230), Cutaneous squamous cell carcinoma (MESH:D002294), Tumor (MESH:D009369), dysplasia (MESH:D015792), Cutaneous Carcinogenesis (MESH:D063646)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** FVB/N — Mus musculus (Mouse), Transformed cell line (CVCL_C0MX)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11277703/full.md

## References

53 references — full list in the complete paper: https://tomesphere.com/paper/PMC11277703/full.md

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Source: https://tomesphere.com/paper/PMC11277703