Comparative Investigation of DAL-1 Tumor Suppressor Protein Expression in Cancerous and Normal Ovarian Specimens

Document Type : Original Article (s)

Authors

1 Associate Professor, Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Student of Medicine, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: DAL-1 (differentially expressed in adenocarcinoma of the lung-1), located on chromosome 18 (18p11.3), has been identified as a tumor suppressor gene. DAL-1 is one member of cell adhesion molecules, play role in cytoskeleton organization with intracellular tight junctions. Inactivation of this gene can destroy the intracellular and cell-cytoskeleton adhesion, which induces malignancy and metastasis. We aimed to compare the DAL-1 tumor suppressor protein expression in cancerous and normal ovarian specimens.Methods:  60 samples of ovarian cancer and 60 adjacent normal tissues from the same tumor samples were used. Immunohistochemistry method used to investigate the expression of DAL-1 protein. For scrutiny of percentage of cells in stained tissue sections, we took advantage of optical microscope and motic advanced plus 2 software. The presence of brown cytoplasm, with or without brown membrane, was considered positive for the expression of DAL-1.Findings: Significantly, expression of DAL-1 protein was reduced in tumoral tissues compared with adjacent normal tissues (P < 0.001). Also, the decrease of protein expression was statistically related with lymph node metastasis (P = 0.036).Conclusion: According to the low incidence of DAL-1 protein in tumor samples compared to normal samples in this study, DAL-1 protein expression can be related with the pathogenesis of ovarian cancer. On the other hand, significantly relation of the absence or reduce expression of this protein in cancerous samples with lymph node metastasis reveals that DAL-1 can be used as a diagnostic marker for ovarian cancer patients. 

Keywords

References

  1. Nussbaum R, McInnes RR, Willard HF. Cancer genetics and genomics. In: Nussbaum R, McInnes RR, Willard HF, editors. Thompson and Thompson genetics in medicine. 6th ed. Philadelphia, PA: W.B. Saunders; 2001. p. 125-50.
  2. Gayet J, Zhou XP, Duval A, Rolland S, Hoang JM, Cottu P, et al. Extensive characterization of genetic alterations in a series of human colorectal cancer cell lines. Oncogene 2001; 20(36): 5025-32.
  3. Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, et al. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 1991; 253(5020): 665-9.
  4. Kinzler KW, Nilbert MC, Su LK, Vogelstein B, Bryan TM, Levy DB, et al. Identification of FAP locus genes from chromosome 5q21. Science 1991; 253(5020): 661-5.
  5. Shahshahan Z. Distribution and staging of 250 patients with ovarian cancer. Iran J Surg 2013; 12(33): 30-4.
  6. Benedet JL, Bender H, Jones H, III, Ngan HY, Pecorelli S. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet 2000; 70(2): 209-62.
  7. Gudmundsdottir K, Ashworth A. The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability. Oncogene 2006; 25(43): 5864-74.
  8. Tran YK, Bogler O, Gorse KM, Wieland I, Green MR, Newsham IF. A novel member of the NF2/ERM/4.1 superfamily with growth suppressing properties in lung cancer. Cancer Res 1999; 59(1): 35-43.
  9. Gutmann DH, Hirbe AC, Huang ZY, Haipek CA. The protein 4.1 tumor suppressor, DAL-1, impairs cell motility, but regulates proliferation in a cell-type-specific fashion. Neurobiol Dis 2001; 8(2): 266-78.
  10. Tsujiuchi T, Sugata E, Masaoka T, Onishi M, Fujii H, Shimizu K, et al. Expression and DNA methylation patterns of Tslc1 and Dal-1 genes in hepatocellular carcinomas induced by N-nitrosodiethylamine in rats. Cancer Sci 2007; 98(7): 943-8.
  11. Uchino K, Ito A, Wakayama T, Koma Y, Okada T, Ohbayashi C, et al. Clinical implication and prognostic significance of the tumor suppressor TSLC1 gene detected in adenocarcinoma of the lung. Cancer 2003; 98(5): 1002-7.
  12. Cannistra SA. Cancer of the ovary. N Engl J Med 2004; 351(24): 2519-29.
  13. Dafou D, Grun B, Sinclair J, Lawrenson K, Benjamin EC, Hogdall E, et al. Microcell-mediated chromosome transfer identifies EPB41L3 as a functional suppressor of epithelial ovarian cancers. Neoplasia 2010; 12(7): 579-89.
  14. Perry A, Cai DX, Scheithauer BW, Swanson PE, Lohse CM, Newsham IF, et al. Merlin, DAL-1, and progesterone receptor expression in clinicopathologic subsets of meningioma: a correlative immunohistochemical study of 175 cases. J Neuropathol Exp Neurol 2000; 59(10): 872-9.
  15. Yu T, Robb VA, Singh V, Gutmann DH, Newsham IF. The 4.1/ezrin/radixin/moesin domain of the DAL-1/Protein 4.1B tumour suppressor interacts with 14-3-3 proteins. Biochem J 2002; 365(Pt 3): 783-9.
  16. Wan M, Sun T, Vyas R, Zheng J, Granada E, Dubeau L. Suppression of tumorigenicity in human ovarian cancer cell lines is controlled by a 2 cM fragment in chromosomal region 6q24-q25. Oncogene 1999; 18(8): 1545-51.
  17. Kruzelock RP, Cuevas BD, Wiener JR, Xu FJ, Yu Y, Cabeza-Arvelaiz Y, et al. Functional evidence for an ovarian cancer tumor suppressor gene on chromosome 22 by microcell-mediated chromosome transfer. Oncogene 2000; 19(54): 6277-85.
  18. Cao Q, Abeysinghe H, Chow O, Xu J, Kaung H, Fong C, et al. Suppression of tumorigenicity in human ovarian carcinoma cell line SKOV-3 by microcell-mediated transfer of chromosome 11. Cancer Genet Cytogenet 2001; 129(2): 131-7.
  19. Stronach EA, Sellar GC, Blenkiron C, Rabiasz GJ, Taylor KJ, Miller EP, et al. Identification of clinically relevant genes on chromosome 11 in a functional model of ovarian cancer tumor suppression. Cancer Res 2003; 63(24): 8648-55.
  20. Yaqinuddin A, Abbas F, Naqvi SZ, Bashir MU, Qazi R, Qureshi SA. Silencing of MBD1 and MeCP2 in prostate-cancer-derived PC3 cells produces differential gene expression profiles and cellular phenotypes. Biosci Rep 2008; 28(6): 319-26.
  21. Yi C, McCarty JH, Troutman SA, Eckman MS, Bronson RT, Kissil JL. Loss of the putative tumor suppressor band 4.1B/Dal1 gene is dispensable for normal development and does not predispose to cancer. Mol Cell Biol 2005; 25(22): 10052-9.
  22. Kobel M, Huntsman D, Gilks CB. Critical molecular abnormalities in high-grade serous carcinoma of the ovary. Expert Rev Mol Med 2008; 10: e22.
  23. Kikuchi S, Yamada D, Fukami T, Masuda M, Sakurai-Yageta M, Williams YN, et al. Promoter methylation of DAL-1/4.1B predicts poor prognosis in non-small cell lung cancer. Clin Cancer Res 2005; 11(8): 2954-61.
  24. Yamada D, Kikuchi S, Williams YN, Sakurai-Yageta M, Masuda M, Maruyama T, et al. Promoter hypermethylation of the potential tumor suppressor DAL-1/4.1B gene in renal clear cell carcinoma. Int J Cancer 2006; 118(4): 916-23.
  25. Schulz WA, Alexa A, Jung V, Hader C, Hoffmann MJ, Yamanaka M, et al. Factor interaction analysis for chromosome 8 and DNA methylation alterations highlights innate immune response suppression and cytoskeletal changes in prostate cancer. Mol Cancer 2007; 6: 14.
Journal of Isfahan Medical School
Volume 31, Issue 250 - Serial Number 250
July and August 2013
Pages 1339-1350

Files

History

  • Receive Date: 23 July 2013
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics