PMID- 26926340 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20181113 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 16 DP - 2016 Feb 29 TI - More expression of BDNF associates with lung squamous cell carcinoma and is critical to the proliferation and invasion of lung cancer cells. PG - 171 LID - 10.1186/s12885-016-2218-0 [doi] LID - 171 AB - BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been reported to promote tumorigenesis and progression in several human malignancies. The purpose of this study was to explore the function of BDNF in lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC). METHODS: The expression of BDNF was examined in 110 samples of lung SCC and ADC by immunohistochemistry. The protein level of BDNF was examined in 25 lung SCC or ADC samples and paired non-tumors by western blot. BDNF expression was also evaluated in human bronchial epithelial cells (HBE) and 4 lung cancer cell lines using western blot. Three BDNF mRNA variants containing exons IV, VI and IX were evaluated in HBE, two SCC (SK, LK2) and two ADC (A549, LTE) cell lines by RT-PCR. The expression and secretion of BDNF were also determined in cells using western blot and ELISA. Then the shRNA specific for BDNF was transfected into LK2 or A549 cells to further elucidate the BDNF knockdown on cell proliferation, apoptosis and invasion, which were confirmed by MTT, flow cytometry and transwell examinations. RESULTS: 71.8 % (79 out of 110) of lung SCC and ADC samples were detected positive BDNF, and high expression of BDNF was significantly correlated with histological type and T stage. Compared with non-tumorous counterparts, BDNF was apparently overexpressed in SCC and ADC tissues. In cell studies, the extensive expression and secretion of BDNF were demonstrated in lung cancer cells compared with HBE cells. Interestingly, the expressions of BDNF mRNA variant IV and VI were identical in all cells examined. However, more expression of BDNF mRNA variant IX was found in SK and LK2 cells. The apoptotic cells were increased, and the cell proliferation and invasion were both attenuated once the expression of BDNF was inhibited. When retreated by rhBDNF, BDNF knockdown cells showed less apoptotic or more proliferative and invasive. CONCLUSIONS: Our data show that BDNF probably facilitates the tumorigenesis of lung SCC and ADC. The expression of BDNF mRNA variant IX is probably more helpful to the upregulation of BDNF in SCC, and intervening the production of BDNF could be a possible strategy to lung cancer therapy. FAU - Zhang, Si-Yang AU - Zhang SY AD - Center of Laboratory Technology and Experimental Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, People's Republic of China. neko200321063@126.com. FAU - Hui, Lin-Ping AU - Hui LP AD - Laboratory Center, the Fourth Affiliated Hospital of China Medical University, No.4 Chongshan East Road, Huanggu District, Shenyang, Liaoning, People's Republic of China. 46236572@qq.com. FAU - Li, Chun-Yan AU - Li CY AD - Center of Laboratory Technology and Experimental Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, People's Republic of China. 1753027976@qq.com. FAU - Gao, Jian AU - Gao J AD - Center of Laboratory Technology and Experimental Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, People's Republic of China. cmulab@qq.com. FAU - Cui, Ze-Shi AU - Cui ZS AD - Center of Laboratory Technology and Experimental Medicine, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, People's Republic of China. labczs@mail.cmu.edu.cn. FAU - Qiu, Xue-Shan AU - Qiu XS AD - Department of Pathology, the First Affiliated Hospital of China Medical University, No.155 Nanjing North Street, Heping District, Shenyang, Liaoning, People's Republic of China. qiuxues@hotmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160229 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) SB - IM MH - Adenocarcinoma/genetics/metabolism/pathology MH - Apoptosis/genetics MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Carcinoma, Squamous Cell/genetics/*metabolism/pathology MH - Cell Line, Tumor MH - Cell Proliferation MH - Gene Expression MH - Gene Expression Regulation, Neoplastic MH - Gene Knockdown Techniques MH - Humans MH - Immunohistochemistry MH - Lung Neoplasms/genetics/*metabolism/pathology MH - Neoplasm Grading MH - Neoplasm Metastasis MH - Neoplasm Staging MH - RNA, Messenger/genetics/metabolism MH - RNA, Small Interfering/genetics MH - Tumor Burden PMC - PMC4772289 EDAT- 2016/03/02 06:00 MHDA- 2016/12/15 06:00 PMCR- 2016/02/29 CRDT- 2016/03/02 06:00 PHST- 2015/09/20 00:00 [received] PHST- 2016/02/24 00:00 [accepted] PHST- 2016/03/02 06:00 [entrez] PHST- 2016/03/02 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] PHST- 2016/02/29 00:00 [pmc-release] AID - 10.1186/s12885-016-2218-0 [pii] AID - 2218 [pii] AID - 10.1186/s12885-016-2218-0 [doi] PST - epublish SO - BMC Cancer. 2016 Feb 29;16:171. doi: 10.1186/s12885-016-2218-0.