TY - JOUR AB - Sunitinib, a tyrosine kinase inhibitor, is among the first‑line treatments for metastatic or advanced stage renal cell carcinoma (RCC). However, patients with RCC develop resistance to sunitinib. We have previously demonstrated that lysosome‑associated membrane protein 2 (LAMP‑2), which has three splice variants with different functions (LAMP‑2A, LAMP‑2B, and LAMP‑2C), is involved in RCC. In the present study, we examined which splice variants of LAMP‑2 contributed to sunitinib resistance in RCC cells. In vitro analysis using ACHN, human RCC cell line, revealed that the IC50 of sunitinib was significantly increased by overexpression of LAMP‑2A and LAMP‑2B, but not LAMP‑2C (P<0.01). Kaplan‑Meier survival analysis using clinical samples revealed an association between shorter survival and high expression of LAMP‑2A and LAMP‑2B, but not LAMP‑2C, in patients with RCC treated with sunitinib (P=0.01). Furthermore, high expression of LAMP‑2A and LAMP‑2B in RCC revealed a weak to moderate inverse correlation with the tumor shrinkage rate and progression‑free survival, respectively. Thus, high expression of LAMP‑2A and LAMP‑2B contributed to the acquisition of sunitinib resistance, indicating that the expression of these two variants can predict the efficacy of sunitinib treatment in patients with RCC. AD - Division of Urology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8503, Japan Division of Experimental Pathology, Faculty of Medicine, Tottori University, Yonago, Tottori 683‑8503, Japan Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187‑8502, Japan AU - Nishikawa,Ryoma AU - Osaki,Mitsuhiko AU - Sasaki,Ryo AU - Ishikawa,Mizuho AU - Yumioka,Tetsuya AU - Yamaguchi,Noriya AU - Iwamoto,Hideto AU - Honda,Masashi AU - Kabuta,Tomohiro AU - Takenaka,Atsushi AU - Okada,Futoshi DA - 2020/11/01 DO - 10.3892/or.2020.7752 EP - 1820 IS - 5 JO - Oncol Rep KW - drug resistance renal cell carcinoma lysosome‑associated membrane proteins 2 sunitinib splice site variant PY - 2020 SN - 1021-335X 1791-2431 SP - 1810 ST - Splice variants of lysosome‑associated membrane proteins 2A and 2B are involved in sunitinib resistance in human renal cell carcinoma cells T2 - Oncology Reports TI - Splice variants of lysosome‑associated membrane proteins 2A and 2B are involved in sunitinib resistance in human renal cell carcinoma cells UR - https://doi.org/10.3892/or.2020.7752 VL - 44 ER -