Vol 3, No 4 (2018)
Original article
Published online: 2018-12-19

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A preliminary study on MTDH expression as a potential prognostic cancer marker

Katarzyna Kaminska1, Sylwia Szablewska2, Krzysztof Roszkowski2, Marzena Anna Lewandowska3
Medical Research Journal 2018;3(4):211-214.

Abstract

Background: Clinical studies have revealed that MTDH is overexpressed in various malignancies and
is associated with disease progression and poor clinical outcomes. In order to study MTDH prognostic
potential, we decided to evaluate MTDH expression changes using cancerous and non-cancerous cells
lines. Secondly, for the first time, we evaluated MTDH expression in prostate cancer cell lines representing
different metastatic potential in vivo.


Methods: MTDH and PBGD (control) genes expression were measured by reverse transcription-quantitative
polymerase chain reaction assay using Universal Probe Library in cancerous and non-cancerous cell lines.

Results: MTDH gene expression analysis showed a decrease in colorectal cancer cell lines (Caco2, HT29)
compared to non-cancerous cells lines (VH10, VH25, Hek293). The mean level of the MTDH mRNA expression,
normalized in relation to the reference gene PBGD, increased in the prostate cancer cell lines
as follows: PC3 (0.62 ± 0.07), PC3M (1.02 ± 0.17), PC3MPro4 (1.20 ± 0.22), and reached the highest
value in PC3M4 (1.86 ± 0.48). In VH10, the expression of this gene was at 1.0 ± 0.07.

Conclusions: Our MTDH gene expression data are consistent with Mtdh protein expression analyzed in
The Human Protein Atlas (HPA). Increasing MTDH expression is a promising prognostic factor.

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References

  1. Garraway LA, Widlund HR, Rubin MA, et al. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature. 2005; 436(7047): 117–122.
  2. Li Y, Zou L, Li Q, et al. Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer. Nat Med. 2010; 16(2): 214–218.
  3. van 't Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002; 415(6871): 530–536.
  4. Hu G, Chong RA, Yang Q, et al. MTDH activation by 8q22 genomic gain promotes chemoresistance and metastasis of poor-prognosis breast cancer. Cancer Cell. 2009; 15(1): 9–20.
  5. Su Zz, Chen Y, Kang Dc, et al. Identification and cloning of human astrocyte genes displaying elevated expression after infection with HIV-1 or exposure to HIV-1 envelope glycoprotein by rapid subtraction hybridization, RaSH. Oncogene. 2002; 21(22): 3592–3602.
  6. Su Zz, Chen Y, Kang Dc, et al. Customized rapid subtraction hybridization (RaSH) gene microarrays identify overlapping expression changes in human fetal astrocytes resulting from human immunodeficiency virus-1 infection or tumor necrosis factor-alpha treatment. Gene. 2003; 306: 67–78.
  7. Yoo BK, Emdad L, Lee SG, et al. Astrocyte elevated gene-1 (AEG-1): A multifunctional regulator of normal and abnormal physiology. Pharmacol Ther. 2011; 130(1): 1–8.
  8. Emdad L, Sarkar D, Su ZZ, et al. Astrocyte elevated gene-1: recent insights into a novel gene involved in tumor progression, metastasis and neurodegeneration. Pharmacol Ther. 2007; 114(2): 155–170.
  9. Meng X, Thiel KW, Leslie KK. Drug resistance mediated by AEG-1/MTDH/LYRIC. Adv Cancer Res. 2013; 120: 135–157.
  10. Hu G, Wei Y, Kang Y. The multifaceted role of MTDH/AEG-1 in cancer progression. Clin Cancer Res. 2009; 15(18): 5615–5620.
  11. Zhao Y, Moran MS, Yang Q, et al. Metadherin regulates radioresistance in cervical cancer cells. Oncol Rep. 2012; 27(5): 1520–1526.
  12. Pettaway CA, Pathak S, Greene G, et al. Selection of highly metastatic variants of different human prostatic carcinomas using orthotopic implantation in nude mice. Clin Cancer Res. 1996; 2(9): 1627–1636.
  13. Gnosa S, Shen YM, Wang CJ, et al. Expression of AEG-1 mRNA and protein in colorectal cancer patients and colon cancer cell lines. J Transl Med. 2012; 10: 109.
  14. Li J, Zhang Nu, Song LB, et al. Astrocyte elevated gene-1 is a novel prognostic marker for breast cancer progression and overall patient survival. Clin Cancer Res. 2008; 14(11): 3319–3326.
  15. Thirkettle HJ, Girling J, Warren AY, et al. LYRIC/AEG-1 is targeted to different subcellular compartments by ubiquitinylation and intrinsic nuclear localization signals. Clin Cancer Res. 2009; 15(9): 3003–3013.
  16. Emdad L, Sarkar D, Lee SG, et al. Astrocyte elevated gene-1: a novel target for human glioma therapy. Mol Cancer Ther. 2010; 9(1): 79–88.
  17. Thul PJ, Åkesson L, Wiking M, et al. A subcellular map of the human proteome. Science. 2017; 356(6340).
  18. Kikuno N, Shiina H, Urakami S, et al. Knockdown of astrocyte-elevated gene-1 inhibits prostate cancer progression through upregulation of FOXO3a activity. Oncogene. 2007; 26(55): 7647–7655.
  19. Lee HJ, Jung DB, Sohn EJ, et al. Inhibition of Hypoxia Inducible Factor Alpha and Astrocyte-Elevated Gene-1 Mediates Cryptotanshinone Exerted Antitumor Activity in Hypoxic PC-3 Cells. Evid Based Complement Alternat Med. 2012; 2012: 390957.
  20. Erdem H, Yildirim U, Uzunlar AK, et al. Relationship among expression of basic-fibroblast growth factor, MTDH/astrocyte elevated gene-1, adenomatous polyposis coli, matrix metalloproteinase 9,and COX-2 markers with prognostic factors in prostate carcinomas. Niger J Clin Pract. 2013; 16(4): 418–423.