Filamin A inhibits tumor progression through regulating BRCA1 expression in human breast cancer

Guo,Yundi; Li,Ming; Bai,Guanghui; Li,Xiaoning; Sun,Zhongwen; Yang,Jie; Wang,Lu; Sun,Jing

doi:10.3892/ol.2018.9473

Filamin A inhibits tumor progression through regulating BRCA1 expression in human breast cancer

Authors:
- Yundi Guo
- Ming Li
- Guanghui Bai
- Xiaoning Li
- Zhongwen Sun
- Jie Yang
- Lu Wang
- Jing Sun
View Affiliations

Affiliations: Suzhou Vocational Health College, Suzhou, Jiangsu 215009, P.R. China, Suzhou Municipal Hospital, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu 215000, P.R. China
Published online on: September 20, 2018 https://doi.org/10.3892/ol.2018.9473
Pages: 6261-6266
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Filamin A (FlnA) is an actin cross‑linking protein. Previous studies have demonstrated its role in tumor progression in a wide range of cancer types. It has been reported that FlnA interacts with the DNA damage response protein, breast cancer gene 1 (BRCA1), which is a tumor suppressor gene. However, to the best of our knowledge, there are no studies evaluating the association of these genes in human carcinomas. In the present study, the immunohistochemistry of a tissue microarray was used to investigate the clinical significance of FlnA and BRCA1 expression in pathological specimens collected from 424 patients treated for breast cancer. In addition, FlnA and BRCA1 expression was downregulated in the breast cancer cell line, MCF‑7, through FlnA RNA interference. FlnA expression was exhibited by cancer tissues collected from 137 patients with breast cancer, which also exhibited high expression of BRCA1 and were associated with a relatively long survival time. A significant association was identified between FlnA protein expression and tumor size, and between FlnA protein expression and progesterone receptor expression. These results suggest that BRCA1 expression could be regulated by FlnA in the breast cancer cell line, MCF‑7. Overall, the present study demonstrates that FlnA expression was associated with BRAC1 expression and tumor size in breast cancer, which provides important implications for future study of FlnA in the progression of human breast cancer.

View Figures

View References

1	Feng Y and Walsh CA: The many faces of filamin: A versatile molecular scaffold for cell motility and signalling. Nat Cell Biol. 6:1034–1038. 2004. View Article : Google Scholar : PubMed/NCBI
2	Popowicz GM, Schleicher M, Noegel AA and Holak TA: Filamins: Promiscuous organizers of the cytoskeleton. Trends Biochem Sci. 31:411–419. 2006. View Article : Google Scholar : PubMed/NCBI
3	Meng X, Yuan Y, Maestas A and Shen Z: Recovery from DNA damage-induced G2 arrest requires actin-binding protein filamin-A/actin-binding protein 280. J Biol Chem. 279:6098–6105. 2004. View Article : Google Scholar : PubMed/NCBI
4	Duval D, Lardeux A, Le Tourneau T, Norris RA, Markwald RR, Sauzeau V, Probst V, Le Marec H, Levine R, Schott JJ and Merot J: Valvular dystrophy associated filamin A mutations reveal a new role of its first repeats in small-GTPase regulation. Biochim Biophys Acta. 1843:234–244. 2014. View Article : Google Scholar : PubMed/NCBI
5	Nakamura F, Pudas R, Heikkinen O, Permi P, Kilpeläinen I, Munday AD, Hartwig JH, Stossel TP and Ylänne J: The structure of the GPIb-filamin A complex. Blood. 107:1925–3192. 2016. View Article : Google Scholar
6	Shao QQ, Zhang TP, Zhao WJ, Liu ZW, You L, Zhou L, Guo JC and Zhao YP: Filamin A: Insights into its exact role in cancers. Pathol Oncol Res. 22:245–252. 2016. View Article : Google Scholar : PubMed/NCBI
7	Yue J, Lu H, Liu J, Berwick M and Shen Z: Filamin-A as a marker and target for DNA damage based cancer therapy. DNA Repair (Amst). 11:192–200. 2012. View Article : Google Scholar : PubMed/NCBI
8	Savoy RM and Ghosh PM: The dual role of filamin A in cancer: Can't live with (too much of) it, can't live without it. Endocr Relat Cancer. 20:R341–R356. 2013. View Article : Google Scholar : PubMed/NCBI
9	Ford D, Easton DF, Bishop DT, Narod SA and Goldgar DE: Risks of cancer in BRCA1-mutation carriers. Breast cancer linkage consortium. Lancet. 343:692–695. 1994. View Article : Google Scholar : PubMed/NCBI
10	Easton DF, Bishop DT, Ford D and Crockford GP: Genetic linkage analysis in familial breast and ovarian cancer: Results from 214 families. The breast cancer linkage consortium. Am J Hum Genet. 52:678–701. 1993.PubMed/NCBI
11	Gowen LC, Johnson BL, Latour AM, Sulik KK and Koller BH: Brca1 deficiency results in early embryonic lethality characterized by neuroepithelial abnormalities. Nat Genet. 12:191–194. 1996. View Article : Google Scholar : PubMed/NCBI
12	Velkova A, Carvalho MA, Johnson JO, Tavtigian SV and Monteiro AN: Identification of Filamin A as a BRCA1-interacting protein required for efficient DNA repair. Cell Cycle. 9:1421–1433. 2010. View Article : Google Scholar : PubMed/NCBI
13	Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J and Wheeler DL: GenBank. Nucleic Acids Res. 33:D34–D38. 2005. View Article : Google Scholar : PubMed/NCBI
14	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
15	Hartwig JH and Stossel TP: Isolation and properties of actin, myosin, and a new actinbinding protein in rabbit alveolar macrophages. J Biol Chem. 250:5696–5705. 1975.PubMed/NCBI
16	Nakamura F, Stossel TP and Hartwig JH: The filamins: Organizers of cell structure and function. Cell Adh Migr. 5:160–169. 2011. View Article : Google Scholar : PubMed/NCBI
17	Flanagan LA, Chou J, Falet H, Neujahr R, Hartwig JH and Stossel TP: Filamin A the Arp2/3 complex, and the morphology and function of cortical actin filaments in human melanoma cells. J Cell Biol. 155:511–517. 2001. View Article : Google Scholar : PubMed/NCBI
18	Ai J, Huang H, Lv X, Tang Z, Chen M, Chen T, Duan W, Sun H, Li Q, Tan R, et al: FLNA and PGK1 are two potential markers for progression in hepatocellular carcinoma. Cell Physiol Biochem. 27:207–216. 2011. View Article : Google Scholar : PubMed/NCBI
19	Lin JF, Xu J, Tian HY, Gao X, Chen QX, Gu Q, Xu GJ, Song JD and Zhao FK: Identification of candidate prostate cancer biomarkers in prostate needle biopsy specimens using proteomic analysis. Int J Cancer. 121:2596–2605. 2007. View Article : Google Scholar : PubMed/NCBI
20	Jiang X, Yue J, Lu H, Campbell N, Yang Q, Lan S, Haffty BG, Yuan C and Shen Z: Inhibition of filamin-A reduces cancer metastatic potential. Int J Biol Sci. 9:67–77. 2013. View Article : Google Scholar : PubMed/NCBI
21	Alper O, Stetler-Stevenson WG, Harris LN, Leitner WW, Ozdemirli M, Hartmann D, Raffeld M, Abu-Asab M, Byers S, Zhuang Z, et al: Novel anti-filamin-A antibody detects a secreted variant of filamin-A in plasma from patients with breast carcinoma and high-grade astrocytoma. Cancer Sci. 100:1748–1756. 2009. View Article : Google Scholar : PubMed/NCBI
22	Tian HM, Liu XH, Han W, Zhao LL, Yuan B and Yuan CJ: Differential expression of filamin A and its clinical significance in breast cancer. Oncol Lett. 6:681–686. 2013. View Article : Google Scholar : PubMed/NCBI
23	Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM and Ding W: A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 266:66–71. 1994. View Article : Google Scholar : PubMed/NCBI
24	Kim KM, Moon YJ, Park SH, Park HJ, Wang SI, Park HS, Lee H, Kwon KS, Moon WS, Lee DG, et al: Individual and combined expression of DNA damage response molecules PARP1, gammaH2AX, BRCA1, and BRCA2 predict shorter survival of soft tissue sarcoma patients. PLoS One. 11:e01631932016. View Article : Google Scholar : PubMed/NCBI