Title | Initiation of esophageal squamous cell carcinoma (ESCC) in a murine 4-nitroquinoline-1-oxide and alcohol carcinogenesis model. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Osei-Sarfo K, Urvalek AM, Tang X-H, Scognamiglio T, Gudas LJ |
Journal | Oncotarget |
Volume | 6 |
Issue | 8 |
Pagination | 6040-52 |
Date Published | 2015 Mar 20 |
ISSN | 1949-2553 |
Keywords | 4-Nitroquinoline-1-oxide, Animals, Carcinogenesis, Carcinogens, Carcinoma, Squamous Cell, Cell Proliferation, Disease Models, Animal, Esophageal Neoplasms, Esophageal Squamous Cell Carcinoma, Ethanol, Female, Humans, Mice, Mice, Inbred C57BL |
Abstract | Esophageal squamous cell carcinomas (ESCCs) are very common, aggressive tumors, and are often associated with alcohol and tobacco abuse. Because ESCCs exhibit high recurrence rates and are diagnosed at late stages, identification of prognostic and drug targets for prevention and treatment is critical. We used the 4-nitroquinoline-1-oxide (4-NQO) murine model of oral carcinogenesis and the Meadows-Cook model of alcohol abuse to assess changes in the expression of molecular markers during the initial stages of ESCC. Combining these two models, which mimic chronic alcohol and tobacco abuse in humans, we detected increased cellular proliferation (EGFR and Ki67 expression), increased canonical Wnt signaling and downstream elements (β-catenin, FoxM1, and S100a4 protein levels), changes in cellular adhesive properties (reduced E-cadherin in the basal layer of the esophageal epithelium), and increased levels of phosphorylated ERK1/2 and p38. Additionally, we found that treatment with ethanol alone increased the numbers of epithelial cells expressing solute carrier family 2 (facilitated glucose transporter, member 1) (SLC2A1) and carbonic anhydrase IX (CAIX), and increased the phosphorylation of p38. Thus, we identified both 4-NQO- and ethanol-specific targets in the initial stages of esophageal carcinogenesis, which should lead to the development of potential markers and therapeutic targets for human ESCC. |
DOI | 10.18632/oncotarget.3339 |
Alternate Journal | Oncotarget |
PubMed ID | 25714027 |
PubMed Central ID | PMC4467420 |
Grant List | T32 CA062948 / CA / NCI NIH HHS / United States DE010389 / DE / NIDCR NIH HHS / United States T32CA062948 / CA / NCI NIH HHS / United States R01 AA018332 / AA / NIAAA NIH HHS / United States F32 AA0201045 / AA / NIAAA NIH HHS / United States R01 DE010389 / DE / NIDCR NIH HHS / United States R01 AA01832-S1 / AA / NIAAA NIH HHS / United States |