| 2389 Aberrant Hedgehog Signaling Regulates PTHrP Expression in Primary OSCC | ||
|
C. GONZALES1, J. STERLING2, and G. MUNDY2, 1University of Texas San Antonio / Health Science Ctr, USA, 2Vanderbilt University Medical Center, Center for Bone Biology, Nashville, TN, USA Oral Squamous Cell Carcinoma (OSCC) is an aggressive cancer that kills 40% of patients within 5 years of diagnosis. Invasion of the mandible by OSCC is correlated with a decreased disease-free survival period. Shibahara et al., (2005) demonstrated that PTHrP expression in primary OSCC positively correlates with local invasion of the mandible and suggested that invasion of the mandible by OSCC tumor cells is facilitated by stimulating osteoclasts to break down bone. Using QRT-PCR and microarray analysis, we detected PTHrP expression in the OSCC cell lines, Cal27 and SCC4. We have previously found that PTHrP expression by breast cancer cells facilitates metastatic invasion of bone and is dependent on the developmental hedgehog pathway. Accordingly, we confirmed the expression of members of the hedgehog signal transduction pathway including Gli 1, 2, and 3, in Cal27 and SCC4 cell lines using RT-PCR. We hypothesize that PTHrP expression, by primary OSCC, is regulated by the hedgehog signaling. Objective: To determine if Gli 1, 2, and 3 regulate PTHrP expression in OSCC cell lines. Methods: SCC4 cells were transiently transfected with a mammalian expression construct containing the luciferase reporter gene under the control of the PTHrP promoter. Co-transfections were performed with expression constructs for Gli 1, 2, 3, truncated Gli 3 (trGli3) and the dominant-negative Gli 2 Engrailed construct. Luciferase assays were performed to determine if Gli proteins regulate the PTHrP promoter in SCC4 cells. Results: SCC4 cells express endogenous Gli 1, 2, and 3, but no increase in luciferase due to over-expression of Gli proteins activating the PTHrP promoter was detected. However, the trGli 3 and dominant-negative Gli 2 Engrailed construct reduced luciferase expression by 50% and 70% respectively. Conclusions: This study demonstrates that hedgehog signaling regulates PTHrP expression in OSCC cell lines and potentially provides them with the capacity to invade bone. | ||
| Seq #240 - Premalignant Oral Lesions and Oral Cancer 3:30 PM-4:45 PM, Friday, March 23, 2007 Ernest N. Morial Convention Center Exhibit Hall I2-J | ||
|
Back to the Oral Medicine & Pathology Program
| ||