nach oben

Erschienen in:

01.03.2014 | Original Article

shRNA-mediated silencing of ZFX attenuated the proliferation of breast cancer cells

verfasst von: Hongjian Yang, Yue Lu, Yabing Zheng, Xingfei Yu, Xianghou Xia, Xiangming He, Weiliang Feng, Lei Xing, Zhiqiang Ling

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2014

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Breast cancer is the cause for highest number of cancer-related death among women worldwide. This study was focused on investigating the role of zinc-finger protein X-linked (ZFX) in human breast cancer.

Methods

Expression levels of ZFX were analyzed in 99 patients and four breast cancer cell lines. Lentivirus-mediated RNA interference was applied to silence ZFX expression, and the effects of ZFX knockdown on the growth of breast cancer cells were investigated.

Results

The immunohistochemical expression of ZFX was higher in more advanced tumor tissues. ZFX was also overexpressed in multiple breast cancer cell lines. Knockdown of ZFX inhibited cell proliferation and colony formation of MCF-7 and MDA-MB-231 cells. Moreover, ZFX silencing resulted in cell cycle arrest at G0/G1 phase. Depletion of ZFX decreased the phosphorylation level of AKT and increased the phosphorylation level of ERK2 and the expression of cyclin D1, which is involved in cell survival and cell cycle regulation.

Conclusions

These findings suggest that ZFX plays an important role in breast cancer development and could be a potential therapeutic target for breast cancer.

Siegel RN, Jemal D, Jemal A (2012) Cancer statistics, 2012. CA A Cancer J Clin 62:10–29CrossRef

Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70PubMedCrossRef

Storvold GL, Andersen TI, Perou CM, Frengen E (2006) siRNA: a potential tool for future breast cancer therapy? Crit Rev Oncog 12:127–150PubMedCrossRef

Wang YH, Liu S, Zhang G, Zhou CQ, Zhu HX, Zhou XB, Quan LP, Bai LF, Xu NZ (2005) Knockdown of c-Myc expression by RNAi inhibits MCF-7 breast tumor cells growth in vitro and in vivo. Breast Cancer Res 7:R220–R228PubMedCentralPubMedCrossRef

Wang X, Lu H, Urvalek AM, Li T, Yu L, Lamar J, DiPersio CM, Feustel PJ, Zhao J (2011) KLF8 promotes human breast cancer cell invasion and metastasis by transcriptional activation of MMP9. Oncogene 30:1901–1911PubMedCrossRef

Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494–498PubMedCrossRef

Devi GR (2006) siRNA-based approaches in cancer therapy. Cancer Gene Ther 13:819–829PubMedCrossRef

Laity JH, Lee BM, Wright PE (2001) Zinc finger proteins: new insights into structural and functional diversity. Curr Opin Struct Biol 11:39–46PubMedCrossRef

Iwase M, Satta Y, Hirai Y, Hirai H, Imai H, Takahata N (2003) The amelogenin loci span ancient pseudoautosomal boundary in diverse mammalian species. Proc Natl Acad Sci USA 100:5258–5263PubMedCrossRef

10.

Luoh SW, Bain P, Polakiewicz RD, Goodheart M, Gardner H, Jaenisch R, Page DC (1997) Zfx mutation results in small animal size and reduced germ cell number in male and female mice. Development 124:2275–2284PubMed

11.

Huang D, Gao Q, Guo L, Zhang C, Jiang W, Li H, Wang J, Han X, Shi Y, Lu SH (2009) Isolation and identification of cancer stem-like cells in esophageal carcinoma cell lines. Stem Cells Dev 18(3):465–473. doi:10.1089/scd 2008.0033PubMedCrossRef

12.

Tricoli JV, Bracken RB (1993) ZFY gene expression and retention in human prostate adenocarcinoma. Genes Chromosomes Cancer 6(2):65–72PubMedCrossRef

13.

Sakhinia E, Glennie C, Hoyland JA, Menasce LP, Brady G, Miller C, Radford JA, Byers RJ (2007) Clinical quantitation of diagnostic and predictive gene expression levels in follicular and diffuse large B-cell lymphoma by RT-PCR gene expression profiling. Blood 109(9):3922–3928. doi:10.1182/blood-2006-09-046391 PubMedCrossRef

14.

Nikpour P, Emadi-Baygi M, Mohammad-Hashem F, Maracy MR, Haghjooy-Javanmard S (2012) Differential expression of ZFX gene in gastric cancer. J Biosci 37(1):85–90PubMedCrossRef

15.

Arenzana TL, Smith-Raska MR, Reizis B (2009) Transcription factor Zfx controls BCR-induced proliferation and survival of B lymphocytes. Blood 113:5857–5867PubMedCrossRef

16.

Schnabl B, Valletta D, Kirovski G, Hellerbrand C (2011) Zinc finger protein 267 is up-regulated in hepatocellular carcinoma and promotes tumor cell proliferation and migration. Exp Mol Pathol 3:695–701CrossRef

17.

Cobaleda C, Perez-Caro M, Vicente-Duenas C, Sanchez-Garcia I (2007) Function of the zinc-finger transcription factor SNAI2 in cancer and development. Annu Rev Genet 41:41–61PubMedCrossRef

18.

Poloumienko A (2004) Cloning and comparative analysis of the bovine, porcine, and equine sex chromosome genes ZFX and ZFY. Genome 47:74–83PubMedCrossRef

19.

Schneider-Gadicke A, Beer-Romero P, Brown LG, Nussbaum R, Page DC (1989) ZFX has a gene structure similar to ZFY, the putative human sex determinant, and escapes X inactivation. Cell 57:1247–1258PubMedCrossRef

20.

Stewart SA, Dykxhoorn DM, Palliser D, Mizyno H, Yu EY, An DS, Sabatini DM, Chen ISY, Hahn WC, Sharp PA, Weinberg RA, Novina CD (2003) Lentivirus-delivered stable gene silencing by RNAi in primary cells. RNA 9:493–501PubMedCrossRef

21.

Yuan J, Yan R, Krämer A, Eckerdt F, Roller M, Kaufmann M, Strebhardt K (2004) Cyclin B1 depletion inhibits proliferation and induces apoptosis in human tumor cells. Oncogene 23:5843–5852PubMedCrossRef

22.

Kranenburg O, van der Eb AJ, Zantema A (1996) Cyclin D1 is an essential mediator of apoptotic neuronal cell death. EMBO J 15:46–54PubMed

23.

Wu S, Lao XY, Sun TT, Ren LL, Kong X, Wang JL, Wang YC, Du W, Yu YN, Weng YR, Hong J, Fang JY (2013) Knockdown of ZFX inhibits gastric cancer cell growth in vitro and in vivo via downregulating the ERK-MAPK pathway. Cancer Lett 337(2):293–300. doi:10.1016/j.canlet.2013.04.003 PubMedCrossRef

Titel: shRNA-mediated silencing of ZFX attenuated the proliferation of breast cancer cells
verfasst von: Hongjian Yang
Yue Lu
Yabing Zheng
Xingfei Yu
Xianghou Xia
Xiangming He
Weiliang Feng
Lei Xing
Zhiqiang Ling
Publikationsdatum: 01.03.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 3/2014
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-014-2379-y

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

shRNA-mediated silencing of ZFX attenuated the proliferation of breast cancer cells