p73 participates in WWOX-mediated apoptosis in leukemia cells

Lin,Donghong; Cui,Zhaolei; Kong,Lingying; Cheng,Feng; Xu,Jianping; Lan,Fenghua

doi:10.3892/ijmm.2013.1289

p73 participates in WWOX-mediated apoptosis in leukemia cells

Authors:
- Donghong Lin
- Zhaolei Cui
- Lingying Kong
- Feng Cheng
- Jianping Xu
- Fenghua Lan
View Affiliations

Affiliations: Department of Clinical Laboratory, Fujian Medical University, Fuzhou 35004, P.R. China, Department of Pathology, Affiliated People's Hospital of Fujian Province, Fujian University of Tradition Chinese Medicine, Fuzhou 350004, P.R. China, Department of Clinical Laboratory, Affiliated Second People's Hospital, Fujian University of Tradition Chinese Medicine, Fuzhou 350003, P.R. China, Department of Clinical Genetics and Experimental Medicine, Fuzhou General Hospital, Fujian Medical University, Fuzhou 350025, P.R. China
Published online on: February 26, 2013 https://doi.org/10.3892/ijmm.2013.1289
Pages: 849-854

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

The WWOX gene is considered to be a tumor-suppressor gene which encodes a protein (Wwox) implicated in various types of solid human cancers. It has been shown that overexpression of WWOX in human tumors promotes apoptosis in vitro and suppresses tumor growth in vivo. Recently, we investigated the effects of WWOX overexpression in vitro and observed marked growth arrest in human leukemia cells; however, the underlying mechanism(s) for this effect is unknown. The present study aimed to elucidate the primary mechanism(s) underlying WWOX-mediated apoptosis in human leukemia. We traced the interactions between WWOX and its associated factors p73 and p53 after WWOX overexpression was induced in Jurkat and K562 cells. Our data revealed that p73 participates in WWOX-mediated apoptosis in Jurkat and K562 cells through binding with Wwox in the cytoplasm without a nuclear-cytoplasmic translocation.

View Figures

View References

1	Bednarek AK, Laflin KJ, Daniel RL, Liao Q, Hawkins KA and Aldaz CM: WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3–24.1, a region frequently affected in breast cancer. Cancer Res. 60:2140–2145. 2000.PubMed/NCBI
2	Ried K, Finnis M, Hobson L, et al: Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells. Hum Mol Genet. 9:1651–1663. 2000. View Article : Google Scholar : PubMed/NCBI
3	Del Mare S, Salah Z and Aqeilan RI: WWOX: its genomics, partners, and functions. J Cell Biochem. 108:737–745. 2009.PubMed/NCBI
4	Macias MJ, Wiesner S and Sudol M: WW and SH3 domains, two different scaffolds to recognize proline-rich ligands. FEBS Lett. 513:30–37. 2002. View Article : Google Scholar : PubMed/NCBI
5	Nunez MI, Ludes-Meyers J and Aldaz CM: WWOX protein expression in normal human tissues. J Mol Hist. 37:115–125. 2006. View Article : Google Scholar : PubMed/NCBI
6	Wang X, Chao L, Jin G, Ma G, Zang Y and Sun J: Association between CpG island methylation of the WWOX gene and its expression in breast cancers. Tumour Biol. 30:8–14. 2009. View Article : Google Scholar : PubMed/NCBI
7	Guo W, Wang G, Dong Y, Guo Y, Kuang G and Dong Z: Decreased expression of WWOX in the development of esophageal squamous cell carcinoma. Mol Carcinog. Dec 27–2011.(Epub ahead of print).
8	Nakayama S, Semba S, Maeda N, Matsushita M, Kuroda Y and Yokozaki H: Hypermethylation-mediated reduction of WWOX expression in intraductal papillary mucinous neoplasms of the pancreas. Br J Cancer. 100:1438–1443. 2009. View Article : Google Scholar : PubMed/NCBI
9	Dias EP, Pimenta FJ, Sarquis MS, et al: Association between decreased WWOX protein expression and thyroid cancer development. Thyroid. 17:1055–1059. 2007. View Article : Google Scholar : PubMed/NCBI
10	Yang J, Cogdell D, Yang D, et al: Deletion of the WWOX gene and frequent loss of its protein expression in human osteosarcoma. Cancer Lett. 291:31–38. 2010. View Article : Google Scholar : PubMed/NCBI
11	Fabbri M, Iliopoulos D, Trapasso F, et al: WWOX gene restoration prevents lung cancer growth in vitro and in vivo. Proc Natl Acad Sci USA. 102:15611–15616. 2005. View Article : Google Scholar : PubMed/NCBI
12	Iliopoulos D, Fabbri M, Druck T, Qin HR, Han SY and Huebner K: Inhibition of breast cancer cell growth in vitro and in vivo: effect of restoration of Wwox expression. Clin Cancer Res. 13:268–274. 2007. View Article : Google Scholar : PubMed/NCBI
13	Aqeilan RI, Trapasso F, Hussain S, et al: Targeted deletion of Wwox reveals a tumor-suppressor function. Proc Natl Acad Sci USA. 104:3949–3954. 2007. View Article : Google Scholar : PubMed/NCBI
14	Aqeilan RI, Pekarsky Y, Herrero JJ, et al: Functional association between Wwox tumor suppressor protein and p73, a p53 homolog. Proc Natl Acad Sci USA. 101:4401–4406. 2004. View Article : Google Scholar : PubMed/NCBI
15	Hezova R, Ehrmann J and Kolar Z: WWOX, a new potential tumor suppressor gene. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 151:11–15. 2007. View Article : Google Scholar : PubMed/NCBI
16	Yang JL and Zhang W: WWOX tumor suppressor gene. Histol Histopathol. 23:877–882. 2008.
17	Chang NS, Hsu LJ, Lin YS, Lai FJ and Sheu HM: WW domain-containing oxidoreductase: a candidate tumor suppressor. Trends Mol Med. 13:12–22. 2007. View Article : Google Scholar : PubMed/NCBI
18	Gomes CC, Diniz MG, Oliveira CS, Tavassoli M, Odell EW, Gomez RS and De Marco L: Impact of WWOX alterations on p73, ΔNp73, p53, cell proliferation and DNA ploidy in salivary gland neoplasms. Oral Dis. 17:564–571. 2011.
19	Aqeilan RI, Kuroki T, Pekarsky Y, et al: Loss of WWOX expression in gastric carcinoma. Clin Cancer Res. 10:3053–3058. 2004. View Article : Google Scholar : PubMed/NCBI
20	Alsop AE, Taylor K, Zhang J, Gabra H, Paige AJ and Edwards PA: Homozygous deletions may be markers of nearby heterozygous mutations: the complex deletion at FRA16D in the HCT116 colon cancer cell line removes exons of WWOX. Genes Chromosomes Cancer. 47:437–447. 2008. View Article : Google Scholar
21	Żelazowski MJ, Płuciennik E, Pasz-Walczak G, Potemski P, Kordek R and Bednarek AK: WWOX expression in colorectal cancer: a real-time quantitative RT-PCR study. Tumour Biol. 32:551–560. 2011.PubMed/NCBI
22	Qin HR, Iliopoulos D, Semba S, et al: A role for the WWOX gene in prostate cancer. Cancer Res. 66:6477–6480. 2006. View Article : Google Scholar : PubMed/NCBI
23	Ishii H and Furukawa Y: Alterations of common chromosome fragile sites in hematopoietic malignancies. Int J Hematol. 79:238–242. 2004. View Article : Google Scholar : PubMed/NCBI
24	Ishii H, Vecchione A, Furukawa Y, et al: Expression of FRA16D/WWOX and FRA3B/FHIT genes in hematopoietic malignancies. Mol Cancer Res. 1:940–947. 2003.PubMed/NCBI
25	Watanabe A, Hippo Y, Taniguchi H, et al: An opposing view on WWOX protein function as a tumor suppressor. Cancer Res. 63:8629–8633. 2003.PubMed/NCBI
26	Chang NS: A potential role of p53 and WOX1 in mitochondrial apoptosis (Review). Int J Mol Med. 9:19–24. 2002.PubMed/NCBI
27	Aqeilan RI, Donati V, Palamarchuk A, et al: WW domain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function. Cancer Res. 65:6764–6772. 2005. View Article : Google Scholar : PubMed/NCBI