title: Lactotransferrin expression is downregulated and affects the mitogen-activated protein kinase pathway in gastric cancer.
abstract: Gastric cancer (GC) is the second leading cause of cancer-associated mortality worldwide. In advanced and metastatic GC, conventional chemotherapy results in limited efficacy and the average survival rate is currently approximately 10 months. Dysregulated activation of numerous genes, including zinc finger, DHHC-type containing 14; caspase-associated recruitment domain-containing protein; and Ras association domain family member 10, have been implicated in GC. The tumor suppressor function of lactotransferrin (LTF) has been reported in a variety of tumors, including GC, nasopharyngeal carcinoma (NPC) and prostate cancer. However, the mechanism of the tumor suppressor function of LTF in GC remains unclear. In the present study, the expression levels of LTF in patient GC tissue samples were investigated using reverse transcription-quantitative polymerase chain reaction, and it was demonstrated that the LTF mRNA expression level in GC tissue samples was reduced by ~20-fold compared with the adjacent non-cancerous tissues (t=4.56, P<0.01). A similar trend in LTF protein expression was observed by western blot analysis. Furthermore, the present study demonstrated that the mitogen-activated protein kinase (MAPK) signaling pathway intermediates p38,c-Jun N-terminal kinase (JNK) andc-Jun were highly expressed in GC tissue samples, and indicated that LTF downregulation may be associated with the dysregulation of the MAPK signaling pathway in GC tissues. In addition, the present study indicated that LTF overexpression reduced the expression of p38, JNK2 andc-Jun in the GC cell line, SGC7901. The present study demonstrates that LTF expression is downregulated in GC tissues and that LTF may serve an important role in the dysregulation of the MAPK signaling pathway.
authors.affiliation: Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Gengqiu
authors.initials: G
authors.lastname: Luo
authors.affiliation: Molecular Genetics Laboratory, Cancer Research Institute, Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Molecular Genetics Laboratory, Cancer Research Institute, Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.affiliation: Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yi
keywords: expression; gastric cancer; lactotransferrin; mitogen-activated protein kinase