Low Zip 4 gene expression levels in RPMI - 8226 and ARH - 77 cell lines support the possible role of zip 4 transporter protein in plasma cell tumorogenesis
Abstract
Abstract
Aim. Multiple myeloma and plasma cell leukemia are cancers of plasma cells. Multiple myeloma rarely transforms to plasma cell leukemia during the progression period. Zinc as a chemical element modulates proliferation and differentiation of cells by affecting several growth factors. Zip 4 modifies zinc metabolism in a cell as a transporter protein. While high Zip 4 gene expression was found in pancreas and hepatocellular carcinoma, low Zip 4 gene expression was observed in prostate carcinoma. Methods. Here, Zip 4 expression levels were studied in RPMI - 8226 and ARH - 77 cell lines as examples of multiple myeloma and plasma cell leukemia, respectively. Results. We found lower Zip 4 gene expression levels in both cell lines than that of the normal control (0,000157 in RPMI - 8226, 0,000227 in ARH - 77 cell lines and 1 in normal control) The findings were statistically significant (P < 0.05). The expression levels of Zip 4 gene in both cell lines were approximately similar. No statistical significance was found between the expression levels of Zip 4 in both cell lines (P = 0.547). Conclusion. The results of this study support the possible role of Zip 4 gene expression in plasma cell dyscrasias. The similar result of Zip 4 gene expression level in both cell lines has no role in the transformation of multiple myeloma to plasma cell leukemia.
Keywords: Zip 4 gene, gene expression, multiple myeloma, plasma cell leukemia
Özet
Amaç. Mltipl myelom ve plazma hücreli lösemi, plazma hücresinden köken alan kanserlerdir. Hastalığın ileri evresinde multipl myelom nadiren plazma hücreli lösemi formuna döner. Kimyasal bir element olarak çinko farklı büyüme faktörleri üzerinden memeli hücrelerinde çoğalma ve farklılaşmayı düzenler. Taşıyıcı bir protein olarak Zip 4 ise hücrede çinko metabolizmasında aktif rol alır. Pankreas ve karaciğer kanserlerinde artmış Zip 4 gen ekspresyonu bulunurken, prostat kanserinde düşük Zip 4 gen ekspresyonu tanımlanmaktadır. Yöntemler. Bu çalışmada, sırası ile multipl myelom ve plazma hücreli lösemilere örnek olabilecek RPMI - 8226 ve ARH - 77 hücre hatlarında Zip 4 gen ekspresyon düzeyleri bakılmıştır. Bulgular. Her iki hücre hattında Zip 4 gen ekspresyon düzeyi normale göre daha düşüktür (RPMI - 8226 hücre hattında 0,000157 ve ARH - 77 hücre hattında 0,000227). Elde edilen veriler istatistiksel olarak anlamlıdır (P < 0,05). Her iki hücre hattında Zip 4 gen ekspresyon düzeyleri birbirine çok yakın olarak bulunmuştur. Aralarında istatistiksel olarak anlamlı bir fark da bulunmamıştır (P = 0,547). Sonuç. Sonuçlar plazma hücre diskrazilerinde Zip 4 gen ekspresyonunun olası rolünü destekler niteliktedir. Her iki hücre hattında birbirine yakın bulunan Zip 4 gen ekpresyon düzeyinin multipl myelomanın plazma hücreli lösemiye dönüşmesinde rolü olmadığını ortaya koymaktadır.
Anahtar sözcükler: Zip 4 geni, gen ekspresyonu, multipl myelom, plazma hücreli lösemi
References
- Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC. Multiple myeloma. Lancet 2009; 374: 324-39.
- Lorsbach RB, Hsi ED, Dogan A, Fend F. Plasma cell myeloma and related neoplasms. Am J Clin Pathol 2011; 136: 168-82.
- Albarracin F, Fonseca R. Plasma cell leukemia. Blood Rev 2011; 25: 107-12. Berg JM, Shi Y. The galvanization of biology: A growing appreciation for the roles of zinc. Science 1996; 271: 1081-5.
- Haase H, Rink L. Functional Significance of Zinc-Related Signaling Pathways in Immune Cells. Annu Rev Nutr 2009; 29: 133-52.
- Kambe T, Weaver BP, Andrews GK. The genetics of essential metal homeostasis during development. Genesis 2008; 46: 214-28.
- Weaver BP, Zhang Y, Hiscox S, Guo GL, Apte U, Taylor KM, Sheline CT, Wang L, Andrews GK. Zip4 (Slc39a4) expression is activated in hepatocellular carcinomas and functions to repress apoptosis, enhance cell cycle and increase migration. PLoS One 2010; 5.
- Zhang Y, Bharadwaj U, Logsdon CD, Chen C, Yao Q, Li M. ZIP4 regulates pancreatic cancer cell growth by activating IL-6/STAT3 pathway through zinc finger transcription factor CREB. Clin Cancer Res 2010; 16: 1423-30.
- Chen QG, Zhang Z, Yang Q, Shan GY, Yu XY, Kong CZ. The role of zinc transporter ZIP4 in prostate carcinoma. Urol Oncol 2012; 30: 906-11.
- Noble PB, Cutts JH. Separation of blood leukocytes by Ficoll gradient. Can Vet J 1967; 8: 110-1.
- Coban ZD, Avcu F, Ural AU, Akyol M, Güran Ş. Cytotoxic effect of docetaxel on multiple myeloma cell lines (RPMI-8226) as a chemotherapotic agent. Gulhane Med J 2011; 53: 258-63.
- Jou MY, Hall AG, Philipps AF, Kelleher SL, Lönnerdal B. Tissue-specific alterations in zinc transporter expression in intestine and liver reflect a threshold for homeostatic compensation during dietary zinc deficiency in weanling rats. J Nutr 2009; 139: 835-41.
- Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu B, Lin MT, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, IacobuzioDonahue C, Eshleman JR, Kern SE, Hruban RH, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008; 321: 1801-6.
- Parikh AA, Liu WB, Fan F, Stoeltzing O, Reinmuth N, Bruns CJ, Bucana CD, Evans DB, Ellis LM. Expression and regulation of the novel vascular endothelial growth factor receptor neuropilin-1 by epidermal growth factor in human pancreatic carcinoma. Cancer 2003; 98: 720-9.
- Donahue T, Hines OJ. The ZIP4 pathway in pancreatic cancer. Cancer Biol Ther 2010; 9: 243-5.
- Sher T, Miller KC, Deeb G, Lee K, Chanan-Khan A. Plasma cell leukaemia and other aggressive plasma cell malignancies. Br J Haematol 2010; 150: 418-27. Bladé J, Rosiñol L, Cibeira MT, de Larrea CF. Pathogenesis and progression of monoclonal gammopathy of undetermined significance. Leukemia 2008; 22: 1651
Abstract
Amaç. Mltipl myelom ve plazma hücreli lösemi, plazma hücresinden köken alan kanserlerdir. Hastalığın ileri evresinde multipl myelom nadiren plazma hücreli lösemi formuna döner. Kimyasal bir element olarak çinko farklı büyüme faktörleri üzerinden memeli hücrelerinde çoğalma ve farklılaşmayı düzenler. Taşıyıcı bir protein olarak Zip 4 ise hücrede çinko metabolizmasında aktif rol alır. Pankreas ve karaciğer kanserlerinde artmış Zip 4 gen ekspresyonu bulunurken, prostat kanserinde düşük Zip 4 gen ekspresyonu tanımlanmaktadır. Yöntemler. Bu çalışmada, sırası ile multipl myelom ve plazma hücreli lösemilere örnek olabilecek RPMI - 8226 ve ARH - 77 hücre hatlarında Zip 4 gen ekspresyon düzeyleri bakılmıştır. Bulgular. Her iki hücre hattında Zip 4 gen ekspresyon düzeyi normale göre daha düşüktür (RPMI - 8226 hücre hattında 0,000157 ve ARH 77 hücre hattında 0,000227). Elde edilen veriler istatistiksel olarak anlamlıdır (P < 0,05). Her iki hücre hattında Zip 4 gen ekspresyon düzeyleri birbirine çok yakın olarak bulunmuştur. Aralarında istatistiksel olarak anlamlı bir fark da bulunmamıştır (P = 0,547). Sonuç. Sonuçlar plazma hücre diskrazilerinde Zip 4 gen ekspresyonunun olası rolünü destekler niteliktedir. Her iki hücre hattında birbirine yakın bulunan Zip 4 gen ekpresyon düzeyi Zip 4'ün multipl myelomanın plazma hücreli lösemiye dönüşmesinde rolü olmadığını ortaya koymaktadır.
References
- Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC. Multiple myeloma. Lancet 2009; 374: 324-39.
- Lorsbach RB, Hsi ED, Dogan A, Fend F. Plasma cell myeloma and related neoplasms. Am J Clin Pathol 2011; 136: 168-82.
- Albarracin F, Fonseca R. Plasma cell leukemia. Blood Rev 2011; 25: 107-12. Berg JM, Shi Y. The galvanization of biology: A growing appreciation for the roles of zinc. Science 1996; 271: 1081-5.
- Haase H, Rink L. Functional Significance of Zinc-Related Signaling Pathways in Immune Cells. Annu Rev Nutr 2009; 29: 133-52.
- Kambe T, Weaver BP, Andrews GK. The genetics of essential metal homeostasis during development. Genesis 2008; 46: 214-28.
- Weaver BP, Zhang Y, Hiscox S, Guo GL, Apte U, Taylor KM, Sheline CT, Wang L, Andrews GK. Zip4 (Slc39a4) expression is activated in hepatocellular carcinomas and functions to repress apoptosis, enhance cell cycle and increase migration. PLoS One 2010; 5.
- Zhang Y, Bharadwaj U, Logsdon CD, Chen C, Yao Q, Li M. ZIP4 regulates pancreatic cancer cell growth by activating IL-6/STAT3 pathway through zinc finger transcription factor CREB. Clin Cancer Res 2010; 16: 1423-30.
- Chen QG, Zhang Z, Yang Q, Shan GY, Yu XY, Kong CZ. The role of zinc transporter ZIP4 in prostate carcinoma. Urol Oncol 2012; 30: 906-11.
- Noble PB, Cutts JH. Separation of blood leukocytes by Ficoll gradient. Can Vet J 1967; 8: 110-1.
- Coban ZD, Avcu F, Ural AU, Akyol M, Güran Ş. Cytotoxic effect of docetaxel on multiple myeloma cell lines (RPMI-8226) as a chemotherapotic agent. Gulhane Med J 2011; 53: 258-63.
- Jou MY, Hall AG, Philipps AF, Kelleher SL, Lönnerdal B. Tissue-specific alterations in zinc transporter expression in intestine and liver reflect a threshold for homeostatic compensation during dietary zinc deficiency in weanling rats. J Nutr 2009; 139: 835-41.
- Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu B, Lin MT, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, IacobuzioDonahue C, Eshleman JR, Kern SE, Hruban RH, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008; 321: 1801-6.
- Parikh AA, Liu WB, Fan F, Stoeltzing O, Reinmuth N, Bruns CJ, Bucana CD, Evans DB, Ellis LM. Expression and regulation of the novel vascular endothelial growth factor receptor neuropilin-1 by epidermal growth factor in human pancreatic carcinoma. Cancer 2003; 98: 720-9.
- Donahue T, Hines OJ. The ZIP4 pathway in pancreatic cancer. Cancer Biol Ther 2010; 9: 243-5.
- Sher T, Miller KC, Deeb G, Lee K, Chanan-Khan A. Plasma cell leukaemia and other aggressive plasma cell malignancies. Br J Haematol 2010; 150: 418-27. Bladé J, Rosiñol L, Cibeira MT, de Larrea CF. Pathogenesis and progression of monoclonal gammopathy of undetermined significance. Leukemia 2008; 22: 1651
Details
| Primary Language | English |
|---|---|
| Journal Section | Basic Science Research Articles |
| Authors | |
| Publication Date | March 22, 2013 |
| Published in Issue | Year 2013Volume: 35 Issue: 1 |