Abstract
Abstract Gemcitabine as the standard chemotherapy agent to pancreatic cancer has proved effective; however, the response rate remains at 5.4% and the 5-year survival rate is extremely poor. Due to the shortcomings of gemcitabine and the presence of gemcitabine-resistant pancreatic cancer, the development of targeted agents into an anti-neoplastic agent remains a viable option. We have investigated the transforming growth factor-beta (TGF-β), which is known to play a central role in pancreas cell function. We have already observed that the suppression of TGF-β2 induced an unexpected down-regulation of both TGF-β1 and TGF-β3 with concomitant decreases of survival-related signals, such as N-caderin, β-catenin, pp65 in melanoma cell line. Here, two different pancreatic cancer cell lines (HPAC, BxPC3), which have opposite genetic backgrounds (K-ras, p53, Smad4, EGFR), have shown differing sensitivities to the down-regulation of TGF-β2. Through transcriptome analysis, HPAC showed a high expression of TGF-β2, MUC4, HSP27, BMP4 which are deeply related to tumor progression and metastasis and are composed to core signaling complex initiating from TGF-β2. This was confirmed by TGF-β2 down-regulation with gemcitabine to show a greater decrease in survival potential compared to BxPC3. On the contrary, BxPC3, which has more of the mutant type p53, exhibited greater down-regulation of MUC4 by downregulation of p53 compared to that of TGF-β2. Such observations suggest that BxPC3 is composed of a different core signaling pathway, p53-MUC4 rather than TGF-β2-related signalings.In conclusion, it is necessary that the core signaling pathways which are implicated in individual pancreatic carcinogenesis are more specifically considered so that the various gemcitabine-resistant pancreatic cancer cells on the basis of customized treatment can be controlled. Citation Format: Eunkyung Kim, Sujin Kang, So Y. Kim, Dongxu Kang, Seungha Lee, Hye J. Choi, Joo-Hang Kim, Jae Jin Song. Different pancreatic cancer cells have their own core signaling pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 694. doi:10.1158/1538-7445.AM2014-694
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