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Marino F, Orecchia V, Regis G, et al. STAT3β controls inflammatory responses and early tumor onset in skin and colon experimental cancer models. Am J Cancer Res. 2014;4(5):484-94
Marino, F., Orecchia, V., Regis, G., Musteanu, M., Tassone, B., Jon, C., Forni, M., Calautti, E., Chiarle, R., Eferl, R., & Poli, V. (2014). STAT3β controls inflammatory responses and early tumor onset in skin and colon experimental cancer models. American journal of cancer research, 4(5), 484-94.
Marino, Francesca, et al. "STAT3β controls inflammatory responses and early tumor onset in skin and colon experimental cancer models." American journal of cancer research vol. 4,5 (2014): 484-94.
Marino F, Orecchia V, Regis G, Musteanu M, Tassone B, Jon C, Forni M, Calautti E, Chiarle R, Eferl R, Poli V. STAT3β controls inflammatory responses and early tumor onset in skin and colon experimental cancer models. Am J Cancer Res. 2014 Sep 06;4(5):484-94. eCollection 2014. PMID: 25232490; PMCID: PMC4163613.
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Am J Cancer Res. 2014 Sep 06;4(5):484-94. eCollection 2014.

STAT3β controls inflammatory responses and early tumor onset in skin and colon experimental cancer models.

American journal of cancer research

Francesca Marino, Valeria Orecchia, Gabriella Regis, Monica Musteanu, Beatrice Tassone, Cristina Jon, Marco Forni, Enzo Calautti, Roberto Chiarle, Robert Eferl, Valeria Poli

Affiliations

  1. Department of Molecular Biotechnology and Health Sciences, University of Turin Turin, 10126, Italy.
  2. Spanish National Cancer Research Centre (CNIO) 28029 Madrid, Spain.
  3. Department of Molecular Biotechnology and Health Sciences, University of Turin Turin, 10126, Italy ; Departmen of Pathology, Children's Hospital Boston and Harvard Medical School 02115 Boston, USA.
  4. Medical University Vienna & Comprehensive Cancer Center (CCC), Institute for Cancer Research A-1090 Vienna, Austria.

PMID: 25232490 PMCID: PMC4163613

Abstract

Chronic inflammation is a well-recognized pathogenic factor in tumor initiation and progression. Mice lacking the pro-oncogenic transcription factor STAT3 were shown to be protected from both colitis-associated and epidermal cancers induced by the AOM/DSS and DMBA/TPA protocols, respectively. However, these murine models did not distinguish between the two STAT3 isoforms, the full-length STAT3α, believed to exert most pro-oncogenic functions attributed to STAT3, and the shorter STAT3β, often referred to as a dominant-negative, but possessing specific transcriptional activities. Here we assessed the contribution of STAT3β to inflammation-driven tumorigenesis making use of mice lacking this isoform, but still expressing STAT3α (STAT3(Δβ/Δβ)). We show that the lack of STAT3β leads to exacerbated acute responses to both TPA and DSS, thus confirming its anti-inflammatory role. Enhanced inflammation correlates with earlier tumor onset in both the epidermis and the intestine in STAT3(Δβ/Δβ) mice. In contrast, overall tumor development and final tumor burden were unaffected. These results suggest that STAT3β, by limiting inflammation during the initial phases of tumorigenesis, contributes to tissue homeostasis and counteracts malignant transformation and initial tumor growth. Accordingly, the balance between the two STAT3 isoforms, likely determined by the complex signaling networks shaping the tumor microenvironment and driving tumor transformation and progression, is apparently crucial to determine the initial tumor transformation rates in inflammation-associated cancers.

Keywords: AOM/DSS protocol; DMBA/TPA protocol; STAT3 isoforms; STAT3β; colitis-associated cancer; genetically modified mice; inflammation; inflammation-driven tumorigenesis; skin tumorigenesis

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