Journal article
Forced expression of a constitutively active form of Stat3 in mouse epidermis enhances malignant progression of skin tumors induced by two-stage carcinogenesis
Oncogene, v 27(8), pp 1087-1094
14 Feb 2008
PMID: 17700521
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Recently, our laboratory demonstrated that Stat3 is required for the de novo development of chemically-induced skin tumors. We have further investigated the role of Stat3 in epithelial carcinogenesis using mice in which the expression of a constitutively active/ dimerized form of Stat3 ( Stat3C) is targeted to the proliferative compartment of epidermis ( referred to as K5.Stat3C transgenic mice). Keratinocytes from K5. Stat3C mice showed increased survival following exposure to 7,12-dimethyl-benz[ a] anthracene ( DMBA) and enhanced proliferation following exposure to 12-O-tetradecanoylphorbol-13-acetate ( TPA). In two-stage chemical carcinogenesis experiments using DMBA as the tumor initiator and TPA as the promoter, K5. Stat3C mice developed skin tumors witha shorter latency and in much greater number compared to non-transgenic littermates. Remarkably, 100% of the skin tumors that developed in K5. Stat3C transgenic mice bypassed the premalignant stage and were initially diagnosed as carcinoma in situ which rapidly progressed to squamous cell carcinoma ( SCC). These tumors were highly vascularized, poorly differentiated and invasive and loss of expression of K10, filaggrin and E-cadherin was observed by 20 weeks. Finally, overexpression of Stat3C in a papilloma cell line led to enhanced cell migration and enhanced invasion through Matrigel in both the absence and presence of growth factors. In addition to its critical role in early stages of epithelial carcinogenesis, the current study reveals a novel role for Stat3 in driving malignant progression of skin tumors in vivo.
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Details
- Title
- Forced expression of a constitutively active form of Stat3 in mouse epidermis enhances malignant progression of skin tumors induced by two-stage carcinogenesis
- Creators
- K. S. Chan - Univ Texas Dallas, MD Anderson Canc Ctr, Dept Carcinogenesis, Sci Pk Res Div, Smithville, TX 78957 USAS. Sano - The University of Texas MD Anderson Cancer CenterK. Kataoka - The University of Texas MD Anderson Cancer CenterE. Abel - The University of Texas MD Anderson Cancer CenterS. Carbajal - The University of Texas MD Anderson Cancer CenterL. Beltran - The University of Texas MD Anderson Cancer CenterJ. Clifford - Louisiana State University in ShreveportM. Peavey - The University of Texas MD Anderson Cancer CenterJ. Shen - PharmacoGenetics (China)J. DiGiovanni - The University of Texas MD Anderson Cancer Center
- Publication Details
- Oncogene, v 27(8), pp 1087-1094
- Publisher
- Springer Nature
- Number of pages
- 8
- Grant note
- U01 ES11047; ES07784 / NIEHS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) R01HL074352 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) CA16672; UO1 CA05345 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01 HL074352 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) P30CA016672 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30ES007784 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000253136700008
- Scopus ID
- 2-s2.0-39149129602
- Other Identifier
- 991020202230404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Genetics & Heredity
- Oncology