Year 2018, Volume 57 , Issue 3, Pages 157 - 162 2018-09-14

Significant increase in ZNF304 and decrease in CXCR4 gene expressions may alter anoikis in prostate cancer
ZNF304 gen ifadesinde artış ve CXCR4’de azalma ile prostat kanserinde anoikis değişebilir

Şule AYLA [1] , Gülperi ÖKTEM [2] , Cüneyd PARLAYAN [3]

Aim: To analyze genes that may increase or inhibit the anoikis mechanism between prostate cancer cell line and prostate normal epithelial cell line and examine the possible role of cancer in cancer development.

Materials and Methods: Human prostate epithelial cell line (RWPE) and prostate cancer cell line (DU145) were acquired from ATCC. Both cell lines were maintanied in RPMI 1640 (Biological Industries) medium. Total RNA were isolated and fragmented. Adapters were ligated to prepare RNA library for whole trasncriptome experiments. Statistics and bioinformatics analysis including mapping, clustering, sequencing were done by using Genomics Workbench v 8. (Qiagen) software.

Results: As we compared the normal prostate ephitalial cells (RWPE) and prosatate cancer cells (DU 145); ZNF304,PYCARD ve NOTCH3 were significantly (p<0.05) up-regulated in DU145 cells, on the other hand, CXCR4, PAK3, SERPINB1 genes were significantly down-regulated.

Conclusion: We found that there are significant differential gene expressions in DU-145 cells which may lead to metastatic state via evasion of anoikis process.

Amaç: Prostat kanser hücre hattı (DU145) ve prostat normal epitel hücre hatları (RWPE) arasında anoikis mekanizmasını arttıracak veya inhibe edebilecek genlerin analizini yapmak ve kanser gelişiminde olası rolünü incelemek.
Gereç ve Yöntem: İnsan prostat epitel hücre hattı (RWPE) ve prostat kanseri hücre hatları (DU-145) Amerikan Tip Kültür Koleksiyonu (ATCC)’den temin edildi. Hücre hatlarının çoğaltılmasında ve sürdürülmesinde RPMI 1640 (Biological Industries) besi ortamı kullanıldı. Transkriptom analizi için RNA izolasyonu yapılarak, kütüphane oluşturuldu, kütüphanenin kantitasyonunun ardından NextSeq500 (illumina) ile sekanslama yapıldı. Dizileme, haritalandırma, bağıl gen ifadeleri ölçümleri gibi biyoinformatik analizler Genomics Workbench v 8 (Qiagen) yazılımı kullanılarak GRCh38 referans sekansı ile yapılmıştır.

Bulgular: RWPE Normal prostat epitel hücre kültürleri ile DU145 prostat kanser hücreleri karşılaştırıldığı zaman DU-145 prostat kanser hücre kültürlerinde, ZNF304, PYCARD ve Notch3 gen expresyonlarında anlamlı bir artış (p<0,05) görülürken, CXCR4, Pak3, SerpınB1 gen ekspresyonlarında anlamlı bir azalma (p<0,05) görülmüştür.
Sonuç: DU145 prostat kanseri hücre hattında anoikis ile ilişkili önemli gen ekpresyonlarında artış ve azalma gözlemledik. Değişime bağlı olarak hücrelerin anoikisden kaçarak metastatik özellik kazanabileceğini düşündük

  • Sethi N, Kang Y. Unravelling the complexity of metastasis - molecular understanding and targeted therapies. Nat Rev Cancer 2011;11(10):735-48.
  • Chang YS, di Tomaso E, McDonald DM, Jones R, Jain RK, Munn LL. Mosaic blood vessels in tumors: Frequency of cancer cells in contact with flowing blood. Proc Natl Acad Sci U S A 2000;97(26):14608-13.
  • Glinsky VV, Glinsky GV, Glinskii OV, et al. Intravascular metastatic cancer cell homotypic aggregation at the sites of primary attachment to the endothelium. Cancer Res 2003;63(13):3805-11.
  • Berezovskaya O, Schimmer AD, Glinskii AB, et al. Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells. Cancer Res 2005;65(6):2378-86.
  • Frisch SM, Francis H. Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol 1994;124(4):619-26.
  • Polakowska RR, Piacentini M, Bartlett R, Goldsmith LA, Haake AR. Apoptosis in human skin development: Morphogenesis, periderm, and stem cells. Dev Dyn 1994;199(3):176-88.
  • Hall PA, Coates PJ, Ansari B, Hopwood D. Regulation of cell number in the mammalian gastrointestinal tract: The importance of apoptosis. J Cell Sci 1994;107( Pt 12):3569-77.
  • Coucouvanis E, Martin GR. Signals for death and survival: A two-step mechanism for cavitation in the vertebrate embryo. Cell 1995;83(2):279-87.
  • Chiarugi P, Giannoni E. Anoikis: A necessary death program for anchorage-dependent cells. Biochem Pharmacol 2008;76(11):1352-64.
  • Rosenblatt J, Raff MC, Cramer LP. An epithelial cell destined for apoptosis signals its neighbors to extrude it by an actin- and myosin-dependent mechanism. Curr Biol 2001;11(23):1847-57.
  • Buchheit CL, Weigel KJ, Schafer ZT. Cancer cell survival during detachment from the ECM: Multiple barriers to tumour progression. Nat Rev Cancer 2014;14(9):632-41.
  • Cao Z, Livas T, Kyprianou N. Anoikis and EMT: Lethal "liaisons" during cancer progression. Crit Rev Oncog 2016;21(3-4):155-68.
  • Farris JC, Pifer PM, Zheng L, Gottlieb E, Denvir J, Frisch SM. Grainyhead-like 2 reverses the metabolic changes induced by the oncogenic epithelial-mesenchymal transition: Effects on anoikis. Mol Cancer Res 2016;14(6):528-38.
  • Frisch SM, Screaton RA. Anoikis mechanisms. Curr Opin Cell Biol 2001;13(5):555-62.
  • Reddig PJ, Juliano RL. Clinging to life: Cell to matrix adhesion and cell survival. Cancer Metastasis Rev 2005;24(3):425-39.
  • Simpson CD, Anyiwe K, Schimmer AD. Anoikis resistance and tumor metastasis. Cancer Lett 2008;272(2):177-85.
  • Deng G, Ma L, Meng Q, Ju X, et al. Notch signaling in the prostate: Critical roles during development and in the hallmarks of prostate cancer biology. J Cancer Res Clin Oncol 2016;142(3):531-47.
  • Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136(5):E359-86.
  • Shou J, Ross S, Koeppen H, de Sauvage FJ, Gao WQ. Dynamics of notch expression during murine prostate development and tumorigenesis. Cancer Res 2001;61(19):7291-7.
  • Danza G, Di Serio C, Ambrosio MR, Sturli N, Lonetto G, Rosati F et al. Notch3 is activated by chronic hypoxia and contributes to the progression of human prostate cancer. Int J Cancer 2013;133(11):2577-86.
  • Rajasekhar VK, Studer L, Gerald W, Socci ND, Scher HI. Tumour-initiating stem-like cells in human prostate cancer exhibit increased NF-kappaB signalling. Nat Commun 2011;18(2):162.
  • Aslan B, Monroig P, Hsu MC, et al. The ZNF304-integrin axis protects against anoikis in cancer. Nat Commun 2015;17(6):7351.
  • Bowen NJ, Walker LD, Matyunina LV, et al. Gene expression profiling supports the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as ovarian cancer initiating cells. BMC Med Genomics 2009;2(1):71.
  • Casey T, Patel O, Dykema K, Dover H, Furge K, Plaut K. Molecular signatures reveal circadian clocks may orchestrate the homeorhetic response to lactation. PLoS One 2009;4(10):e7395.
  • Kim YN, Koo KH, Sung JY, Yun UJ, Kim H. Anoikis resistance: An essential prerequisite for tumor metastasis. Int J Cell Biol 2012;2012:306879.
  • Jenning S, Pham T, Ireland SK, Ruoslahti E, Biliran H. Bit1 in anoikis resistance and tumor metastasis. Cancer Lett 2013;333(2):147-51.
  • Frisch SM, Ruoslahti E. Integrins and anoikis. Curr Opin Cell Biol 1997;9(5):701-6.
  • Lee YC, Jin JK, Cheng CJ, et al. Targeting constitutively activated beta1 integrins inhibits prostate cancer metastasis. Mol Cancer Res 2013;11(4):405-17.
  • Davalieva K, Kostovska IM, Kiprijanovska S, et al. Proteomics analysis of malignant and benign prostate tissue by 2D DIGE/MS reveals new insights into proteins involved in prostate cancer. Prostate 2015;75(14):1586-600.
  • Loison F, Xu Y, Luo HR. Proteinase 3 and Serpin B1: A novel pathway in the regulation of caspase-3 activation, neutrophil spontaneous apoptosis, and inflammation. Inflamm Cell Signal 2014;1(6):e462.
  • Rosenbaum E, Begum S, Brait M, et al. AIM1 promoter hypermethylation as a predictor of decreased risk of recurrence following radical prostatectomy. Prostate 2012;72(10):1133-9.
  • Balkwill F. The significance of cancer cell expression of the chemokine receptor CXCR4. Semin Cancer Biol 2004;14(3):171-9.
  • Balkwill F. Cancer and the chemokine network. Nat Rev Cancer 2004;4(7):540-50.
  • Zhang S, Qi L, Li M, et al. Chemokine CXCL12 and its receptor CXCR4 expression are associated with perineural invasion of prostate cancer. J Exp Clin Cancer Res 2008;4(27):62.
  • Akashi T, Koizumi K, Tsuneyama K, Saiki I, Takano Y, Fuse H. Chemokine receptor CXCR4 expression and prognosis in patients with metastatic prostate cancer. Cancer Sci 2008;99(3):539-42.
  • Taichman RS, Cooper C, Keller ET, Pienta KJ, Taichman NS, McCauley LK. Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. Cancer Res 2002;62(6):1832-7.
  • Schioppa T, Uranchimeg B, Saccani A, et al. Regulation of the chemokine receptor CXCR4 by hypoxia. J Exp Med 2003;198(9):1391-402.
  • Helbig G, Christopherson KW 2nd, Bhat-Nakshatri P, et al. NF-kappaB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4. J Biol Chem 2003;278(24):21631-8.
  • Ablett MP, O'Brien CS, Sims AH, Farnie G, Clarke RB. A differential role for CXCR4 in the regulation of normal versus malignant breast stem cell activity. Oncotarget 2014;5(3):599-612.
  • Kochetkova M, Kumar S, McColl SR. Chemokine receptors CXCR4 and CCR7 promote metastasis by preventing anoikis in cancer cells. Cell Death Differ 2009;16(5):664-73.
Primary Language tr
Subjects Health Care Sciences and Services
Journal Section Research Articles

Orcid: 0000-0003-2143-5268
Author: Şule AYLA (Primary Author)
Institution: İstanbul Medipol Üniversitesi Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER), İstanbul
Country: Turkey

Orcid: 0000-0001-6227-9519
Author: Gülperi ÖKTEM
Institution: Ege Üniversitesi Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, İzmir
Country: Turkey

Orcid: 0000-0002-6183-9489
Author: Cüneyd PARLAYAN
Institution: İstanbul Medipol Üniversitesi Doğa Bilimleri ve Mühendislik Fakültesi, Biyomedikal Mühendislik Anabilim Dalı, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER), İstanbul, Türkiye
Country: Turkey


Publication Date : September 14, 2018

Bibtex @research article { etd418162, journal = {Ege Tıp Dergisi}, issn = {1016-9113}, eissn = {2147-6500}, address = {}, publisher = {Ege University}, year = {2018}, volume = {57}, pages = {157 - 162}, doi = {10.19161/etd.418162}, title = {ZNF304 gen ifadesinde artış ve CXCR4’de azalma ile prostat kanserinde anoikis değişebilir}, key = {cite}, author = {Ayla, Şule and Öktem, Gülperi and Parlayan, Cüneyd} }
APA Ayla, Ş , Öktem, G , Parlayan, C . (2018). ZNF304 gen ifadesinde artış ve CXCR4’de azalma ile prostat kanserinde anoikis değişebilir . Ege Tıp Dergisi , 57 (3) , 157-162 . DOI: 10.19161/etd.418162
MLA Ayla, Ş , Öktem, G , Parlayan, C . "ZNF304 gen ifadesinde artış ve CXCR4’de azalma ile prostat kanserinde anoikis değişebilir" . Ege Tıp Dergisi 57 (2018 ): 157-162 <>
Chicago Ayla, Ş , Öktem, G , Parlayan, C . "ZNF304 gen ifadesinde artış ve CXCR4’de azalma ile prostat kanserinde anoikis değişebilir". Ege Tıp Dergisi 57 (2018 ): 157-162
RIS TY - JOUR T1 - ZNF304 gen ifadesinde artış ve CXCR4’de azalma ile prostat kanserinde anoikis değişebilir AU - Şule Ayla , Gülperi Öktem , Cüneyd Parlayan Y1 - 2018 PY - 2018 N1 - doi: 10.19161/etd.418162 DO - 10.19161/etd.418162 T2 - Ege Tıp Dergisi JF - Journal JO - JOR SP - 157 EP - 162 VL - 57 IS - 3 SN - 1016-9113-2147-6500 M3 - doi: 10.19161/etd.418162 UR - Y2 - 2017 ER -
EndNote %0 Ege Tıp Dergisi ZNF304 gen ifadesinde artış ve CXCR4’de azalma ile prostat kanserinde anoikis değişebilir %A Şule Ayla , Gülperi Öktem , Cüneyd Parlayan %T ZNF304 gen ifadesinde artış ve CXCR4’de azalma ile prostat kanserinde anoikis değişebilir %D 2018 %J Ege Tıp Dergisi %P 1016-9113-2147-6500 %V 57 %N 3 %R doi: 10.19161/etd.418162 %U 10.19161/etd.418162
ISNAD Ayla, Şule , Öktem, Gülperi , Parlayan, Cüneyd . "ZNF304 gen ifadesinde artış ve CXCR4’de azalma ile prostat kanserinde anoikis değişebilir". Ege Tıp Dergisi 57 / 3 (September 2018): 157-162 .
AMA Ayla Ş , Öktem G , Parlayan C . ZNF304 gen ifadesinde artış ve CXCR4’de azalma ile prostat kanserinde anoikis değişebilir. ETD. 2018; 57(3): 157-162.
Vancouver Ayla Ş , Öktem G , Parlayan C . ZNF304 gen ifadesinde artış ve CXCR4’de azalma ile prostat kanserinde anoikis değişebilir. Ege Tıp Dergisi. 2018; 57(3): 157-162.