Wenzheng Fang1, Jianxin Qian2, Qing Wu3, Ying Chen4, Guanzhen Yu5. 1. Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China; Department of Oncology, Fuzhou General Hospital, Fuzhou, Fujian Province, People's Republic of China. 2. Department of Medical Oncology, East Hepatobiliary Surgery Hospital, Shanghai, People's Republic of China. 3. Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China. 4. Department of Pathology, Changhai Hospital, Shanghai, People's Republic of China. 5. Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China. Electronic address: qiaoshanqian@aliyun.com.
Abstract
BACKGROUND: The ADAMs proteases are a multifunctional family of proteins, many of which participate in the pathogenesis of cancers. The expression and regulation of ADAMs has not yet been fully examined in gastric cancer. MATERIALS AND METHODS: Using reverse transcription-PCR, messenger RNA expression of ADAM-9, ADAM-10, ADAM-11, ADAM-12, ADAM-15, ADAM-17, ADAM-28, and ADAM-33 was detected in gastric cancer. ADAM-10, ADAM-17, ADAM-28, and FoxM1 expression in gastric cancer was detected by Western blot and immunohistochemistry. The correlation between ADAM-17 and FoxM1 was analyzed in vivo and in vitro. RESULTS: The messenger RNA levels of ADAM-9, ADAM-10, ADAM-15, ADAM-17, ADAM-28, and ADAM-33 were increased in tumor tissues compared with adjacent normal tissue, especially ADAM-10, ADAM-17, and ADAM-28. FoxM1 expression correlated significantly with ADAM-17 expression. FoxM1 regulates ADAM-17 expression in vivo and in vitro, which in turn influences proliferation and tumor growth of gastric cancer cells. Furthermore, Cox regression analysis revealed that FoxM1 and ADAM-17 are independent prognostic factors for patients with gastric cancer. CONCLUSIONS: These results indicate that overexpression of ADAMs may contribute to gastric cancer progression and that ADAM-17 is a downstream target of FoxM1. Overall, the present study highlights the potential for FoxM1 and ADAMs as potential therapeutic targets for patients with gastric carcinoma.
BACKGROUND: The ADAMs proteases are a multifunctional family of proteins, many of which participate in the pathogenesis of cancers. The expression and regulation of ADAMs has not yet been fully examined in gastric cancer. MATERIALS AND METHODS: Using reverse transcription-PCR, messenger RNA expression of ADAM-9, ADAM-10, ADAM-11, ADAM-12, ADAM-15, ADAM-17, ADAM-28, and ADAM-33 was detected in gastric cancer. ADAM-10, ADAM-17, ADAM-28, and FoxM1 expression in gastric cancer was detected by Western blot and immunohistochemistry. The correlation between ADAM-17 and FoxM1 was analyzed in vivo and in vitro. RESULTS: The messenger RNA levels of ADAM-9, ADAM-10, ADAM-15, ADAM-17, ADAM-28, and ADAM-33 were increased in tumor tissues compared with adjacent normal tissue, especially ADAM-10, ADAM-17, and ADAM-28. FoxM1 expression correlated significantly with ADAM-17 expression. FoxM1 regulates ADAM-17 expression in vivo and in vitro, which in turn influences proliferation and tumor growth of gastric cancer cells. Furthermore, Cox regression analysis revealed that FoxM1 and ADAM-17 are independent prognostic factors for patients with gastric cancer. CONCLUSIONS: These results indicate that overexpression of ADAMs may contribute to gastric cancer progression and that ADAM-17 is a downstream target of FoxM1. Overall, the present study highlights the potential for FoxM1 and ADAMs as potential therapeutic targets for patients with gastric carcinoma.