IADR Abstract Archives
Does Heat Shock Protein 70 Alter Squamous Cell Carcinoma Development?
Objectives: Oral carcinoma is one of the most common cancers in the world. Complications associated with head and neck squamous cell carcinoma (SCC) and its treatment significantly impact an individual’s quality of life. Identifying mechanisms that can protect against SCC would have global health benefits. It is well recognized that SCC development is a multistage process, whereby cells evolve from normal to tumor formation. Inducible heat shock protein 70 (Hsp70) is a conserved cytoprotective protein. Previous studies suggest opposing roles for Hsp70 in SCC. As a tumor promoter, Hsp70 can stabilize defective p53 and promote anti-apoptotic pathways. As a cytokine, however, Hsp70 has anti-cancer activity. Using an experimental model of SCC and a novel Hsp70 transgenic mouse line, we explored whether continuous Hsp70 expression prior to SCC induction would reduce the incidence and/or severity of 4-nitroquinoline-1-oxide (4-NQO)-induced SCC.
Methods: At 7-8 weeks old, female Hsp70 transgenic mice (TG; n=17) and their non-transgenic littermates (NTG; n=20) were randomly divided into 3 water-treatment groups: normal water, 1.25% propylene glycol-water (PG/H2O), and 4NQO-PG/H20 (50 ug/ml). Mice received their respective treatments for 16 weeks, followed by normal waterfor 6 weeks. Weekly body weights and oral examinations for tumor appearance and size were documented. Excised tongues and salivary glands were examined histologically for dysplasia, SCC and Hsp70 production. Data wereanalyzed using multiple t-tests.
Results: Body weights were inversely related to tumor burden. By 20 weeks, 100% of NTG and 90% of TG mice had oral lesions. Onset of visible oral lesions occurredearlier in the TG compared to the NTG, 8 vs. 15 weeks, respectively.
Conclusions: We successfully replicated a murine model of SCC using Hsp70 transgenic mice; preliminary data support a role for Hsp70 promoting carcinogenesis. Further studies will examine the cellular response to 4NQO in Hsp70 transgenic mice.
Methods: At 7-8 weeks old, female Hsp70 transgenic mice (TG; n=17) and their non-transgenic littermates (NTG; n=20) were randomly divided into 3 water-treatment groups: normal water, 1.25% propylene glycol-water (PG/H2O), and 4NQO-PG/H20 (50 ug/ml). Mice received their respective treatments for 16 weeks, followed by normal waterfor 6 weeks. Weekly body weights and oral examinations for tumor appearance and size were documented. Excised tongues and salivary glands were examined histologically for dysplasia, SCC and Hsp70 production. Data wereanalyzed using multiple t-tests.
Results: Body weights were inversely related to tumor burden. By 20 weeks, 100% of NTG and 90% of TG mice had oral lesions. Onset of visible oral lesions occurredearlier in the TG compared to the NTG, 8 vs. 15 weeks, respectively.
Conclusions: We successfully replicated a murine model of SCC using Hsp70 transgenic mice; preliminary data support a role for Hsp70 promoting carcinogenesis. Further studies will examine the cellular response to 4NQO in Hsp70 transgenic mice.