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Pancreatic Ductal Adenocarcinoma and Transcription Factors: Role of c-Myc

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Abstract

Introduction

Deregulated expression/activation of transcription factors is a key event in the establishment and progression of human cancer. Furthermore, most oncogenic signaling pathways converge on sets of transcription factors that ultimately control gene expression patterns resulting in cancer development, progression, and metastasis.

Methods

Ductal pancreatic adenocarcinoma (PDA) is the main type of pancreatic cancer and the fourth leading cause of cancer mortality in the Western world. The early stage of the disease is characterized by pancreatic intraepithelial neoplasia lesions bearing mutations in the K-RAS proto-oncogene, which progress to malignant PDA by accumulating additional mutations in the tumor suppressor gene CDKN2A (p16) and in SMAD4 and TP53 transcription factors. The involvement of other signaling pathways in PDA development and progression is an active area of research which may help to clarify the critical steps of this devastating disease.

Results

In this regard, several in vitro and in vivo data have demonstrated the contribution of the transcription factor c-Myc to pancreatic carcinogenesis although the molecular mechanisms are poorly understood. c-Myc is a proto-oncogene which has a pivotal function in growth control, differentiation and apoptosis and is known to act as a downstream transcriptional effector of many signaling pathways involved in these processes. It is regulated at multiple levels and its abnormal expression contributes to the genesis of many human tumors.

Conclusions

This review focuses on the role of c-Myc in pancreatic embryonic development and homeostasis as well as its involvement on pancreatic tumorigenesis. Evidences showing that c-Myc function is highly dose and cell context dependent, together with its recently demonstrated ability to reprogram somatic cells towards a pluripotent stem cell-like state, indicate that the role of c-Myc in pancreas pathophysiology might have been previously underscored.

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Acknowledgments

A.S. and P.N. are supported by Instituto de Salud Carlos III and Departament de Sanitat de la Generalitat de Catalunya, I.H-M is supported by Instituto de Salud Carlos III. Work in the authors’ laboratories was supported by grants from Fundació La MaratóTV3 (grant 051110) to PN, from Generalitat de Catalunya (2009SGR1409) to PN, from Instituto de Salud Carlos III (CP04/00292) to IH-M, and from Instituto de Salud Carlos III-FEDER (PI080511 to AS; PI05/1912 to IH-M and PI080421 to PN).

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Correspondence to Pilar Navarro.

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Anouchka Skoudy and Inmaculada Hernández-Muñoz contributed equally to the work.

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Skoudy, A., Hernández-Muñoz, I. & Navarro, P. Pancreatic Ductal Adenocarcinoma and Transcription Factors: Role of c-Myc. J Gastrointest Canc 42, 76–84 (2011). https://doi.org/10.1007/s12029-011-9258-0

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