Bax-interacting factor-1 inhibits cell proliferation and promotes apoptosis in prostate cancer cells

Xu,Lin; Wang,Zhu; He,Shan-Yang; Zhang,Su-Fen; Luo,Hong-Jiao; Zhou,Kai; Li,Xiao-Fei; Qiu,Shao-Peng; Cao,Kai-Yuan

doi:10.3892/or.2016.5172

Bax-interacting factor-1 inhibits cell proliferation and promotes apoptosis in prostate cancer cells

Authors:
- Lin Xu
- Zhu Wang
- Shan-Yang He
- Su-Fen Zhang
- Hong-Jiao Luo
- Kai Zhou
- Xiao-Fei Li
- Shao-Peng Qiu
- Kai-Yuan Cao
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Affiliations: Research Center for Clinical Laboratory Standard, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, P.R. China, Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, P.R. China, Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P.R. China
Published online on: October 14, 2016 https://doi.org/10.3892/or.2016.5172
Pages: 3513-3521

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Abstract

Prostate cancer (PCa) is one of the most common malignant tumors and the second leading cause of cancer-related death among males. Bax-interacting factor-1 (Bif-1) is a member of Endophilin family, which binds to and activates the BAX protein in response to the apoptosis signaling pathway. Loss of Bif-1 may suppress the intrinsic pathway of apoptosis and promote tumorigenesis, but there is also converse evidence that Bif-1 could in part be responsible for the tumorigenesis and the role of Bif-1 in PCa development is not clear. In the present study, we aimed to understand the relationships between Bif-1 expression and PCa development. The mRNA and protein expression levels of Bif-1 in PCa cell lines, benign prostatic hyperplasia (BPH) (n=100) and PCa tissues (n=100, including low Gleason-scored PCa n=43 and high Gleason-scored PCa n=57) were detected and the effects of Bif-1 overexpression on the apoptosis, proliferation and migration in LNCaP cells were explored. Bif-1 mRNA levels of PCa cell lines were analyzed by real-time PCR and the protein levels were detected by western blotting. Bif-1 expression in BPH and PCa samples was detected by immunohistochemistry. To build Bif-1 overexpression PCa cells, Bif-1 gene was transfected into LNCaP cells by pcDNA3.1(+)‑Bif-1 vector. Cell apoptosis was detected by flow cytometric analysis, cell proliferation measured by 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay and cell migration was analyzed by wound‑healing assay. The results proved that Bif-1 is downregulated in both PCa cell lines (P<0.01) and clinical samples (P<0.05), and Bif-1 expression is suppressed with the cancer progression (BPH vs. PCa P<0.01, and low Gleason-scored PCa vs. high Gleason-scored PCa P<0.05). Overexpression of Bif-1 could significantly inhibit cell proliferation (P<0.05) and enhancing PCa cell apoptosis (P<0.05), but it did not affect the migration ability (P>0.05). Our findings give strong evidence that Bif-1 is involved in PCa tumorigenesis and acts as a suppressor in PCa progression, and may have significance in understanding the process of PCa development.

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1	McDavid K, Lee J, Fulton JP, Tonita J, Thompson TD, Ferlay J, Brawley O and Bray F: Prostate cancer incidence and mortality rates and trends in the United States and Canada. Public Health Rep. 119:174–186. 2004.PubMed/NCBI
2	Bono AV: The global state of prostate cancer: Epidemiology and screening in the second millennium. BJU Int. 94:(Suppl 3). S1–S2. 2004. View Article : Google Scholar
3	Torre LA, Sauer AM, Chen MS Jr, Kagawa-Singer M, Jemal A and Siegel RL: Cancer statistics for Asian Americans, Native Hawaiians, and Pacific Islanders, 2016: Converging incidence in males and females. CA Cancer J Clin. 66:182–202. 2016. View Article : Google Scholar : PubMed/NCBI
4	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI
5	Kontos CK, Adamopoulos PG and Scorilas A: Prognostic and predictive biomarkers in prostate cancer. Expert Rev Mol Diagn. 15:1567–1576. 2015. View Article : Google Scholar : PubMed/NCBI
6	Chao OS and Clément MV: Epidermal growth factor and serum activate distinct pathways to inhibit the BH3 only protein BAD in prostate carcinoma LNCaP cells. Oncogene. 25:4458–4469. 2006. View Article : Google Scholar : PubMed/NCBI
7	Wen S, Niu Y, Lee SO and Chang C: Androgen receptor (AR) positive vs negative roles in prostate cancer cell deaths including apoptosis, anoikis, entosis, necrosis and autophagic cell death. Cancer Treat Rev. 40:31–40. 2014. View Article : Google Scholar : PubMed/NCBI
8	Coppola D, Oliveri C, Sayegh Z, Boulware D, Takahashi Y, Pow-Sang J, Djeu JY and Wang HG: Bax-interacting factor-1 expression in prostate cancer. Clin Genitourin Cancer. 6:117–121. 2008. View Article : Google Scholar : PubMed/NCBI
9	Castilla C, Congregado B, Chinchón D, Torrubia FJ, Japón MA and Sáez C: Bcl-xL is overexpressed in hormone-resistant prostate cancer and promotes survival of LNCaP cells via interaction with proapoptotic Bak. Endocrinology. 147:4960–4967. 2006. View Article : Google Scholar : PubMed/NCBI
10	Shukla S, Fu P and Gupta S: Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70-Bax interaction in prostate cancer. Apoptosis. 19:883–894. 2014. View Article : Google Scholar : PubMed/NCBI
11	Zhang X, Bi L, Ye Y and Chen J: Formononetin induces apoptosis in PC-3 prostate cancer cells through enhancing the Bax/Bcl-2 ratios and regulating the p38/Akt pathway. Nutr Cancer. 66:656–661. 2014. View Article : Google Scholar : PubMed/NCBI
12	Takahashi Y, Meyerkord CL and Wang HG: Bif-1/endophilin B1: A candidate for crescent driving force in autophagy. Cell Death Differ. 16:947–955. 2009. View Article : Google Scholar : PubMed/NCBI
13	Schlauder SM, Calder KB, Khalil FK, Passmore L, Mathew RA and Morgan MB: Bif-1 and Bax expression in cutaneous Merkel cell carcinoma. J Cutan Pathol. 36:21–25. 2009. View Article : Google Scholar : PubMed/NCBI
14	Cuddeback SM, Yamaguchi H, Komatsu K, Miyashita T, Yamada M, Wu C, Singh S and Wang HG: Molecular cloning and characterization of Bif-1. A novel Src homology 3 domain-containing protein that associates with Bax. J Biol Chem. 276:20559–20565. 2001. View Article : Google Scholar : PubMed/NCBI
15	Takahashi Y, Karbowski M, Yamaguchi H, Kazi A, Wu J, Sebti SM, Youle RJ and Wang HG: Loss of Bif-1 suppresses Bax/Bak conformational change and mitochondrial apoptosis. Mol Cell Biol. 25:9369–9382. 2005. View Article : Google Scholar : PubMed/NCBI
16	Coppola D, Khalil F, Eschrich SA, Boulware D, Yeatman T and Wang HG: Down-regulation of Bax-interacting factor-1 in colorectal adenocarcinoma. Cancer. 113:2665–2670. 2008. View Article : Google Scholar : PubMed/NCBI
17	Lee JW, Jeong EG, Soung YH, Nam SW, Lee JY, Yoo NJ and Lee SH: Decreased expression of tumour suppressor Bax-interacting factor-1 (Bif-1), a Bax activator, in gastric carcinomas. Pathology. 38:312–315. 2006. View Article : Google Scholar : PubMed/NCBI
18	Fan R, Miao Y, Shan X, Qian H, Song C, Wu G, Chen Y and Zha W: Bif-1 is overexpressed in hepatocellular carcinoma and correlates with shortened patient survival. Oncol Lett. 3:851–854. 2012.PubMed/NCBI
19	Iacopino F, Angelucci C, Lama G, Zelano G, La Torre G, D'Addessi A, Giovannini C, Bertaccini A, Macaluso MP, Martorana G, et al: Apoptosis-related gene expression in benign prostatic hyperplasia and prostate carcinoma. Anticancer Res. 26:1849–1854. 2006.PubMed/NCBI
20	Runkle KB, Meyerkord CL, Desai NV, Takahashi Y and Wang HG: Bif-1 suppresses breast cancer cell migration by promoting EGFR endocytic degradation. Cancer Biol Ther. 13:956–966. 2012. View Article : Google Scholar : PubMed/NCBI
21	Mendonca MS, Howard KL, Farrington DL, Desmond LA, Temples TM, Mayhugh BM, Pink JJ and Boothman DA: Delayed apoptotic responses associated with radiation-induced neoplastic transformation of human hybrid cells. Cancer Res. 59:3972–3979. 1999.PubMed/NCBI
22	Bonner AE, Lemon WJ, Devereux TR, Lubet RA and You M: Molecular profiling of mouse lung tumors: Association with tumor progression, lung development, and human lung adenocarcinomas. Oncogene. 23:1166–1176. 2004. View Article : Google Scholar : PubMed/NCBI
23	Coppola D, Helm J, Ghayouri M, Malafa MP and Wang HG: Down-regulation of Bax-interacting factor 1 in human pancreatic ductal adenocarcinoma. Pancreas. 40:433–437. 2011. View Article : Google Scholar : PubMed/NCBI
24	Ho J, Kong JW, Choong LY, Loh MC, Toy W, Chong PK, Wong CH, Wong CY, Shah N and Lim YP: Novel breast cancer metastasis-associated proteins. J Proteome Res. 8:583–594. 2009. View Article : Google Scholar : PubMed/NCBI
25	Ko YH, Cho YS, Won HS, An HJ, Sun DS, Hong SU, Park JH and Lee MA: Stage-stratified analysis of prognostic significance of Bax-interacting factor-1 expression in resected colorectal cancer. Biomed Res Int. 2013:3298392013. View Article : Google Scholar : PubMed/NCBI
26	Kim SY, Oh YL, Kim KM, Jeong EG, Kim MS, Yoo NJ and Lee SH: Decreased expression of Bax-interacting factor-1 (Bif-1) in invasive urinary bladder and gallbladder cancers. Pathology. 40:553–557. 2008. View Article : Google Scholar : PubMed/NCBI
27	Hoimes CJ and Kelly WK: Redefining hormone resistance in prostate cancer. Ther Adv Med Oncol. 2:107–123. 2010. View Article : Google Scholar : PubMed/NCBI
28	Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O and Bray F: International variation in prostate cancer incidence and mortality rates. Eur Urol. 61:1079–1092. 2012. View Article : Google Scholar : PubMed/NCBI
29	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
30	Wang DB, Uo T, Kinoshita C, Sopher BL, Lee RJ, Murphy SP, Kinoshita Y, Garden GA, Wang HG and Morrison RS: Bax interacting factor-1 promotes survival and mitochondrial elongation in neurons. J Neurosci. 34:2674–2683. 2014. View Article : Google Scholar : PubMed/NCBI
31	Yang J, Takahashi Y, Cheng E, Liu J, Terranova PF, Zhao B, Thrasher JB, Wang HG and Li B: GSK-3beta promotes cell survival by modulating Bif-1-dependent autophagy and cell death. J Cell Sci. 123:861–870. 2010. View Article : Google Scholar : PubMed/NCBI