Heterogeneity of Gene Expression in Murine Squamous Cell Carcinoma Development—The Same Tumor by Different Means

Noam Cohen,Shoshana Klein,Nataly Kravchenko-Balasha,Alexander Levitzki,Christian Schönbach

doi:10.1371/journal.pone.0057748

Noam Cohen, Shoshana Klein + Show 3 more

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https://doi.org/10.1371/journal.pone.0057748

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Journal: PloS one	Publication Date: Mar 18, 2013
Citations: 36	License type: CC BY 4.0

Affiliation: Hebrew University of Jerusalem

Abstract

Transformation is a complex process, involving many changes in the cell. In this work, we investigated the transcriptional changes that arose during the development of squamous cell carcinoma (SCC) in mice. Using microarray analysis, we looked at gene expression during different stages in cancer progression in 31 mice. By analyzing tumor progression in each mouse separately, we were able to define the global changes that were common to all 31 mice, as well as significant changes that occurred in fewer individuals. We found that different genes can contribute to the tumorigenic process in different mice, and that there are many ways to acquire the malignant properties defined by Hanahan and Weinberg as “hallmarks of cancer”. Eventually, however, all these changes lead to a very similar cancerous phenotype. The finding that gene expression is strongly heterogeneous in tumors that were induced by a standardized protocol in closely related mice underscores the need for molecular characterization of human tumors and personalized therapy.

Highlights

Cancer is a collection of more than 100 different diseases, and each of these diseases consists of several variants that can develop differently in different individuals
Skin tumors were induced on dorsal back skin of the resulting FVBBX mice by treatment with dimethyl benzanthracene (DMBA) and tetradecanoyl-phorbol acetate (TPA)
In order to examine the role of heterogeneity in tumor progression in the individual mice, we looked at the specific transcripts that were significantly up-regulated or down-regulated between carcinoma and normal skin

Summary

Introduction

Cancer is a collection of more than 100 different diseases, and each of these diseases consists of several variants that can develop differently in different individuals. Tumorigenesis occurs due to changes in the biochemical networks and signaling networks that drive the normal cell. With time the cell accumulates mutations and epigenetic changes, which alter the signaling and biochemical networks, and can lead to cell transformation and cancer [1]. There are a few cases in which a disease can be linked to one major signaling event (e.g. Bcr-Abl in CML [2]), in most tumors this is not the case. Epigenetic and environmental perturbations occur throughout tumor development. The tumor is dependent on several oncogenic signals. The intrinsic genomic instability of cancer cells leads to continual evolution and to intra-tumor heterogeneity [3]

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