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Promyelocytic leukemia zinc finger triggers ATP‑binding cassette subfamily E member 1‑mediated growth inhibition in breast cancer cells

  • Authors:
    • Bandar A. Suliman
    • Suhad Al‑Yahya
  • View Affiliations / Copyright

    Affiliations: BndrGene Medical Center, Research and Consultation Institute, Taibah University, Tayba, Medina 300, Saudi Arabia, Molecular Biomedicine Program, Research Center, King Faisal Specialist Hospital, Riyadh 12713, Saudi Arabia
    Copyright: © Suliman et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Pages: 4143-4150
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    Published online on: July 24, 2018
       https://doi.org/10.3892/ol.2018.9207
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Abstract

The promyelocytic leukemia zinc finger (PLZF) protein is a transcription factor that is involved in a number of biological processes, including those regulating cellular growth; however, little is known regarding how it achieves its inhibitory effect in different cell and tissue types. It has previously been demonstrated that PLZF expression levels become diminished during the oncogenic transformation of certain tissue types and thus, may serve as a hallmark for tumor aggressiveness. To examine this in breast cancer, survival curves from available oncology databases were analyzed and demonstrated that PLZF expression was positively associated with increased survival in patients with breast cancer. The mRNA and protein levels of PLZF were also revealed to be associated with the tumorigenicity of four breast cancer cell lines. Since ATP‑binding cassette subfamily E member 1 (ABCE1), also known as RNase L inhibitor, has been determined to be a target gene of PLZF, the present study also investigated whether the tumor suppressive effect of PLZF was associated with ABCE1 expression. PLZF was revealed to downregulate the expression of ABCE1 in vitro, which relieved the inhibitory effect of ABCE1 on the ribonuclease L enzyme. Finally, it was concluded that PLZF expression caused an ABCE1‑mediated increase in cellular cytotoxicity, as demonstrated by a reduction in the proliferation rate of breast cancer cell lines. The results of the present study are important for understanding how PLZF exerts its final inhibitory actions in breast cancer cells, and potentially in other solid tumors, through the modulation of immunological pathways.
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View References

1 

Chen Z, Brand NJ, Chen A, Chen SJ, Tong JH, Wang ZY, Waxman S and Zelent A: Fusion between a novel Krüppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. EMBO J. 12:1161–1167. 1993.PubMed/NCBI

2 

Li X, Peng H, Schultz DC, Lopez-Guisa JM, Rauscher FJ III and Marmorstein R: Structure-function studies of the BTB/POZ transcriptional repression domain from the promyelocytic leukemia zinc finger oncoprotein. Cancer Res. 59:5275–5282. 1999.PubMed/NCBI

3 

Rho SB, Park YG, Park K, Lee SH and Lee JH: A novel cervical cancer suppressor 3 (CCS-3) interacts with the BTB domain of PLZF and inhibits the cell growth by inducing apoptosis. FEBS Lett. 580:4073–4080. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Park I, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL, Morrison SJ and Clarke MF: Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature. 423:302–305. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Costoya JA, Hobbs RM, Barna M, Cattoretti G, Manova K, Sukhwani M, Orwig KE, Wolgemuth DJ and Pandolfi PP: Essential role of Plzf in maintenance of spermatogonial stem cells. Nat Genet. 36:653–659. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Yeyati PL, Shaknovich R, Boterashvili S, Li J, Ball HJ, Waxman S, Nason-Burchenal K, Dmitrovsky E, Zelent A and Licht JD: Leukemia translocation protein PLZF inhibits cell growth and expression of cyclin A. Oncogene. 18:925–934. 1999. View Article : Google Scholar : PubMed/NCBI

7 

Felicetti F, Errico MC, Bottero L, Segnalini P, Stoppacciaro A, Biffoni M, Felli N, Mattia G, Petrini M, Colombo MP, et al: The promyelocytic leukemia zinc finger-microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms. Cancer Res. 68:2745–2754. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Hurst DR, Edmonds MD, Scott GK, Benz CC, Vaidya KS and Welch DR: Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. Cancer Res. 69:1279–1283. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Bernardo MV, Yelo E, Gimeno L, Campillo JA and Parrado A: Identification of apoptosis-related PLZF target genes. Biochem Biophys Res Commun. 359:317–322. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Cheung M, Pei J, Pei Y, Jhanwar SC, Pass HI and Testa JR: The promyelocytic leukemia zinc-finger gene, PLZF, is frequently downregulated in malignant mesothelioma cells and contributes to cell survival. Oncogene. 29:1633–1640. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Suliman BA, Xu D and Williams BR: The promyelocytic leukemia zinc finger protein: Two decades of molecular oncology. Front Oncol. 2:742012. View Article : Google Scholar : PubMed/NCBI

12 

Savage AK, Constantinides MG, Han J, Picard D, Martin E, Li B, Lantz O and Bendelac A: The transcription factor PLZF directs the effector program of the NKT cell lineage. Immunity. 29:391–403. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Weinreich MA, Odumade OA, Jameson SC and Hogquist KA: PLZF+ T cells regulate memory-like CD8+ T cell development. Nat Immunol. 11:709–716. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Xu D, Holko M, Sadler AJ, Scott B, Higashiyama S, Berkofsky-Fessler W, McConnell MJ, Pandolfi PP, Licht JD and Williams BR: Promyelocytic leukemia zinc finger protein regulates interferon-mediated innate immunity. Immunity. 30:802–816. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Sadler AJ, Suliman BA, Yu L, Yuan X, Wang D, Irving AT, Sarvestani ST, Banerjee A, Mansell AS, Liu JP, et al: The acetyltransferase HAT1 moderates the NF-κB response by regulating the transcription factor PLZF. Nat Commun. 6:67952015. View Article : Google Scholar : PubMed/NCBI

16 

Li XL, Blackford JA, Judge CS, Liu M, Xiao W, Kalvakolanu DV and Hassel BA: RNase-L-dependent Destabilization of Interferon-induced mRNAs. A role for the 2–5A system in attenuation of the interferon response. J Biol Chem. 275:8880–8888. 2000. View Article : Google Scholar : PubMed/NCBI

17 

Zhou A, Paranjape J, Brown TL, Nie H, Naik S, Dong B, Chang A, Trapp B, Fairchild R, Colmenares C and Silverman RH: Interferon action and apoptosis are defective in mice devoid of 2′,5′-oligoadenylate-dependent RNase L. EMBO J. 16:6355–6363. 1997. View Article : Google Scholar : PubMed/NCBI

18 

Fernandes J: Oncogenes: The passport for viral oncolysis through PKR inhibition. Biomark Cancer. 8:101–110. 2016. View Article : Google Scholar : PubMed/NCBI

19 

He Z, Jiang J, Kokkinaki M, Tang L, Zeng W, Gallicano I, Dobrinski I and Dym M: MiRNA-20 and mirna-106a regulate spermatogonial stem cell renewal at the post-transcriptional level via targeting STAT3 and Ccnd1. Stem cells. 31:2205–2217. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Bisbal C, Martinand C, Silhol M, Lebleu B and Salehzada T: Cloning and characterization of a RNAse L inhibitor. A new component of the interferon-regulated 2–5A pathway. J Biol Chem. 270:13308–13317. 1995. View Article : Google Scholar : PubMed/NCBI

21 

McConnell MJ, Chevallier N, Berkofsky-Fessler W, Giltnane JM, Malani RB, Staudt LM and Licht JD: Growth suppression by acute promyelocytic leukemia-associated protein PLZF is mediated by repression of c-myc expression. Mol Cell Biol. 23:9375–9388. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Ren Y, Li Y and Tian D: Role of the ABCE1 gene in human lung adenocarcinoma. Oncol Rep. 27:965–970. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Hendig D, Langmann T, Zarbock R, Schmitz G, Kleesiek K and Götting C: Characterization of the ATP-binding cassette transporter gene expression profile in Y79: A retinoblastoma cell line. Mol Cell Biochem. 328:85–92. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Heimerl S, Bosserhoff AK, Langmann T, Ecker J and Schmitz G: Mapping ATP-binding cassette transporter gene expression profiles in melanocytes and melanoma cells. Melanoma Res. 17:265–273. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Hlavata I, Mohelnikova-Duchonova B, Vaclavikova R, Liska V, Pitule P, Novak P, Bruha J, Vycital O, Holubec L, Treska V, et al: The role of ABC transporters in progression and clinical outcome of colorectal cancer. Mutagenesis. 27:187–196. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A and Chinnaiyan AM: ONCOMINE: A cancer microarray database and integrated data-mining platform. Neoplasia. 6:1–6. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Glass D, Viñuela A, Davies MN, Ramasamy A, Parts L, Knowles D, Brown AA, Hedman AK, Small KS, Buil A, et al: Gene expression changes with age in skin, adipose tissue, blood and brain. Genome Biol. 14:R752013. View Article : Google Scholar : PubMed/NCBI

28 

Bewick V, Cheek L and Ball J: Statistics review 12: Survival analysis. Critical Care. 8:389–394. 2004. View Article : Google Scholar : PubMed/NCBI

29 

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

30 

Suliman BA: The generation of a ZBTB16-inducible expression system in the ACHN adenocarcinoma cell line. J Taibah Univ Medical Sci. 10:359–364. 2015.

31 

Kikugawa T, Kinugasa Y, Shiraishi K, Nanba D, Nakashiro KI, Tanji N, Yokoyama M and Higashiyama S: PLZF regulates Pbx1 transcription and Pbx1-HoxC8 complex leads to androgen-independent prostate cancer proliferation. Prostate. 66:1092–1099. 2006. View Article : Google Scholar : PubMed/NCBI

32 

Mariani F, Sena P, Magnani G, Mancini S, Palumbo C, de Leon Ponz M and Roncucci L: PLZF expression during colorectal cancer development and in normal colorectal mucosa according to body size, as marker of colorectal cancer risk. ScientificWorldJournal. 2013:6308692013. View Article : Google Scholar : PubMed/NCBI

33 

Ali Bandar S: The role of PLZF in the TLR-mediated inflammatory response and the oncogenic characteristics of renal cell carcinoma. 2017.

34 

Paine TM, Soule HD, Pauley RJ and Dawson PJ: Characterization of epithelial phenotypes in mortal and immortal human breast cells. Int J Cancer. 50:463–473. 1992. View Article : Google Scholar : PubMed/NCBI

35 

Nagaraja G, Othman M, Fox B, Alsaber R, Pellegrino C, Zeng Y, Khanna R, Tamburini P, Swaroop A and Kandpal RP: Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: Comprehensive profiles by representational difference analysis, microarrays and proteomics. Oncogene. 25:2328–38. 2006. View Article : Google Scholar : PubMed/NCBI

36 

Xie J, Nair A and Hermiston TW: A comparative study examining the cytotoxicity of inducible gene expression system ligands in different cell types. Toxicology In Vitro. 22:261–266. 2008. View Article : Google Scholar : PubMed/NCBI

37 

Onoda T, Ono T, Dhar DK, Yamanoi A, Fujii T and Nagasue N: Doxycycline inhibits cell proliferation and invasive potential: Combination therapy with cyclooxygenase-2 inhibitor in human colorectal cancer cells. J Lab Clin Med. 143:207–216. 2004. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Suliman BA and Al‑Yahya S: Promyelocytic leukemia zinc finger triggers ATP‑binding cassette subfamily E member 1‑mediated growth inhibition in breast cancer cells. Oncol Lett 16: 4143-4150, 2018.
APA
Suliman, B.A., & Al‑Yahya, S. (2018). Promyelocytic leukemia zinc finger triggers ATP‑binding cassette subfamily E member 1‑mediated growth inhibition in breast cancer cells. Oncology Letters, 16, 4143-4150. https://doi.org/10.3892/ol.2018.9207
MLA
Suliman, B. A., Al‑Yahya, S."Promyelocytic leukemia zinc finger triggers ATP‑binding cassette subfamily E member 1‑mediated growth inhibition in breast cancer cells". Oncology Letters 16.4 (2018): 4143-4150.
Chicago
Suliman, B. A., Al‑Yahya, S."Promyelocytic leukemia zinc finger triggers ATP‑binding cassette subfamily E member 1‑mediated growth inhibition in breast cancer cells". Oncology Letters 16, no. 4 (2018): 4143-4150. https://doi.org/10.3892/ol.2018.9207
Copy and paste a formatted citation
x
Spandidos Publications style
Suliman BA and Al‑Yahya S: Promyelocytic leukemia zinc finger triggers ATP‑binding cassette subfamily E member 1‑mediated growth inhibition in breast cancer cells. Oncol Lett 16: 4143-4150, 2018.
APA
Suliman, B.A., & Al‑Yahya, S. (2018). Promyelocytic leukemia zinc finger triggers ATP‑binding cassette subfamily E member 1‑mediated growth inhibition in breast cancer cells. Oncology Letters, 16, 4143-4150. https://doi.org/10.3892/ol.2018.9207
MLA
Suliman, B. A., Al‑Yahya, S."Promyelocytic leukemia zinc finger triggers ATP‑binding cassette subfamily E member 1‑mediated growth inhibition in breast cancer cells". Oncology Letters 16.4 (2018): 4143-4150.
Chicago
Suliman, B. A., Al‑Yahya, S."Promyelocytic leukemia zinc finger triggers ATP‑binding cassette subfamily E member 1‑mediated growth inhibition in breast cancer cells". Oncology Letters 16, no. 4 (2018): 4143-4150. https://doi.org/10.3892/ol.2018.9207
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