Araştırma Makalesi
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Meme Kanseri Hücrelerinde Zamana Bağlı HIF-2α İfadesi Değişiminin Analizi

Yıl 2017, , 245 - 251, 21.11.2017
https://doi.org/10.29048/makufebed.336876

Öz

Meme kanseri
kadınlarda en sık rastlanan kanser türüdür veTürkiye’de gözlemlenen vaka sayısı
her geçen gün artmaktadır. Meme kanserinin içinde yer aldığı birçok kanser
türünde, kanserli doku kan damarlarından uzak bölgelerde büyürken oksijen
eksikliğine maruz kalır. Hipoksiya olarak adlandırılan bu duruma karşı dokular Hipoksi
ile indüklenebilir faktör (HIF) transkripsiyon faktörlerinin ifade artışı ile
cevap verirler. HIF transkripsiyon faktörlerinin etkisiyle kanserli hücreler,
damar gelişimini uyararak farklı doku ve organlara göç ederler. Bu nedenle HIF
transkripsiyon faktörlerinin hipoksiya sürecindeki değişiminin bilinmesi
önemlidir. HIF-2α hipoksik koşullar altında ifadesi artan bir transkripsiyon
faktörüdür ve farklı kanser türlerinde ifade düzeyi değişiklik göstermektedir.
Bu çalışmanın amacı farklı meme kanseri ve normal meme epiteli hücrelerinde
farklı sürelerde hipoksiya uygulamasının HIF-2α ifadesinin değişimi üzerinde
etkisinin araştırılmasıdır.  

Kaynakça

  • Bardos, J. I., Ashcroft, M. (2005). Negative and positive regulation of HIF-1: a complex network. Biochimica et Biophysica Acta 1755(2): 107–120. http://doi.org/10.1016/j.bbcan.2005.05.001 Beckmann, M. W., Niederacher, D., Schnurch, H. G., Gusterson, B. A., Bender, H. G. (1997). Multistep carcinogenesis of breast cancer and tumour heterogeneity. Journal of Molecular Medicine 75(6): 429–439.
  • Bobarykina, A. I., Minchenko, D. O., Opentanova, I. L., Kovtun, O. O., Komisarenko, S. V, Esumi, H., Minchenko, O. H. (1999). [HIF-1alpha, HIF-2alpha and VHL mRNA expression in different cell lines during hypoxia]. Ukrains’kyi biokhimichnyi zhurnal 78(2): 62–72.
  • Brown, K. D., Lataxes, T. A., Shangary, S., Mannino, J. L., Giardina, J. F., Chen, J., Baskaran, R. (2000). Ionizing radiation exposure results in up-regulation of Ku70 via a p53/ataxia-telangiectasia-mutated protein-dependent mechanism. The Journal of Biological Chemistry 275(9): 6651–6656.
  • Burroughs, S. K., Kaluz, S., Wang, D., Wang, K., Van Meir, E. G., Wang, B. (2013). Hypoxia inducible factor pathway inhibitors as anticancer therapeutics. Future Medicinal Chemistry 5(5): 553–572. http://doi.org/10.4155/fmc.13.17
  • Calzada, M. J., del Peso, L. (2007). Hypoxia-inducible factors and cancer. Clinical & Translational Oncology: Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 9(5): 278–289.
  • Cavadas, M. A. S., Mesnieres, M., Crifo, B., Manresa, M. C., Selfridge, A. C., Scholz, C. C., Taylor, C. T. (2015). REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia, Scientific Reports 5: 17851. http://dx.doi.org/10.1038/srep17851
  • Dukel, M., Streitfeld, W. S., Tang, T. C. C., Backman, L. R. F., Ai, L., May, W. S., Brown, K. D. (2016). The Breast Cancer Tumor Suppressor TRIM29 Is Expressed via ATM-dependent Signaling in Response to Hypoxia. The Journal of Biological Chemistry 291(41): 21541–21552. http://doi.org/10.1074/jbc.M116.730960
  • Hamidian, A., von Stedingk, K., Munksgaard Thoren, M., Mohlin, S., Pahlman, S. (2015). Differential regulation of HIF-1alpha and HIF-2alpha in neuroblastoma: Estrogen-related receptor alpha (ERRalpha) regulates HIF2A transcription and correlates to poor outcome. Biochemical and Biophysical Research Communications 461(3): 560–567.
  • Hu, C.-J., Wang, L.-Y., Chodosh, L. A., Keith, B., Simon, M. C. (2003). Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation. Molecular and Cellular Biology 23(24): 9361–9374. http://doi.org/10.1128/MCB.23.24.9361-9374.2003
  • Jemal, A., Bray, F., Center, M.M., Ferlay, J., Ward, E., Forman, D. (2011). Global Cancer Statistics. American Cancer Society 61: 69-90.
  • Ke, Q., Costa, M. (2006). Hypoxia-inducible factor-1 (HIF-1). Molecular Pharmacology 70(5): 1469–1480. http://doi.org/10.1124/mol.106.027029
  • Keith, B., Johnson, R. S., Simon, M. C. (2011). HIF1α and HIF2α: sibling rivalry in hypoxic tumor growth and progression. Nature Reviews. Cancer 12(1): 9–22. http://doi.org/10.1038/nrc3183
  • Li, Q. F., Wang, X. R., Yang, Y. W., Lin, H. (2006). Hypoxia upregulates hypoxia inducible factor (HIF)-3alpha expression in lung epithelial cells: characterization and comparison with HIF-1alpha. Cell Research 16(6): 548–558. http://doi.org/10.1038/sj.cr.7310072
  • Li, N., Wang, H. X., Qin, C., Wang, X. H., & Han, F. Y. (2015). Relationship between clinicopathological features and HIF-2alpha in gastric adenocarcinoma. Genetics and Molecular Research 14(1): 1404–1413. http://doi.org/10.4238/2015.
  • Liu, Y.-M., Ying, S.-P., Huang, Y.-R., Pan, Y., Chen, W.-J., Ni, L.-Q., Liang, Y. (2016). Expression of HIF-1α and HIF-2α correlates to biological and clinical significance in papillary thyroid carcinoma. World Journal of Surgical Oncology 14: 30. http://doi.org/10.1186/s12957-016-0785-9).
  • Özmen, V. (2009). Breast Cancer in the World and Turkey. J. Breast Health 4: 7-12.
  • Sandlund, J., Ljungberg, B., Wikstrom, P., Grankvist, K., Lindh, G., Rasmuson, T. (2009). Hypoxia-inducible factor-2alpha mRNA expression in human renal cell carcinoma. Acta Oncologica 48(6): 909–914. http://doi.org/10.1080/02841860902824891
  • Semenza, G. L. (2003). Targeting HIF-1 for cancer therapy. Nature Reviews. Cancer 3(10): 721–732. http://doi.org/10.1038/nrc1187
  • Shah, T., Krishnamachary, B., Wildes, F., Mironchik, Y., Kakkad, S. M., Jacob, D., Artemov, D., Bhujwalla, Z. M. (2015). HIF isoforms have divergent effects on invasion, metastasis, metabolism and formation of lipid droplets. Oncotarget 6(29): 28104–28119.
  • Uchida, T., Rossignol, F., Matthay, M. A., Mounier, R., Couette, S., Clottes, E., Clerici, C. (2004). Prolonged hypoxia differentially regulates hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha expression in lung epithelial cells: implication of natural antisense HIF-1alpha. The Journal of Biological Chemistry 279(15): 14871–14878. http://doi.org/10.1074/jbc.M400461200
  • Vaupel, P., Mayer, A. (2007). Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Reviews 26(2): 225–239. http://doi.org/10.1007/s10555-007-9055-1
  • Wang, J.-G., Yuan, L. (2016). HIF-2alpha/Notch3 pathway mediates CoCl2-induced migration and invasion in human breast cancer MCF-7 cells. Acta physiologica Sinica 68(6): 783–789
  • Zhong, H., De Marzo, A. M., Laughner, E., Lim, M., Hilton, D. A., Zagzag, D., Simons, J. W. (1999). Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Research 59(22): 5830–5835.

Analysis of Time-Dependent Alteration of HIF-2α Expression in Breast Cancer Cells

Yıl 2017, , 245 - 251, 21.11.2017
https://doi.org/10.29048/makufebed.336876

Öz

Breast cancer is the
most commonly diagnoised cancer type in women and the number of cases observed
in Turkey has increased day by day. In many types of cancer including breast
cancer, tumor tissues are exposed to oxygen deficiency while growing in areas
distant from blood vessels. Against this condition, knew as hypoxia, tissues respond
via increasing the expression of transcription factors called Hypoxia inducible
factor (HIF). By the effect of HIF transcription factors, cancer cells migrate
to different tissues and organs by stimulating vascular development. Therefore,
it is important to know the change of HIF transcription factors in hypoxia
process. HIF-2
α
is a transcription factor, which is over expressed during hypoxic conditions
and have varies the level of expression in different cancer types. The aim of
this study is that to investigate the effect of time dependent hypoxia exposure
on HIF-2
α expression in different breast cancer cells and normal
breast epithelial cells. 

Kaynakça

  • Bardos, J. I., Ashcroft, M. (2005). Negative and positive regulation of HIF-1: a complex network. Biochimica et Biophysica Acta 1755(2): 107–120. http://doi.org/10.1016/j.bbcan.2005.05.001 Beckmann, M. W., Niederacher, D., Schnurch, H. G., Gusterson, B. A., Bender, H. G. (1997). Multistep carcinogenesis of breast cancer and tumour heterogeneity. Journal of Molecular Medicine 75(6): 429–439.
  • Bobarykina, A. I., Minchenko, D. O., Opentanova, I. L., Kovtun, O. O., Komisarenko, S. V, Esumi, H., Minchenko, O. H. (1999). [HIF-1alpha, HIF-2alpha and VHL mRNA expression in different cell lines during hypoxia]. Ukrains’kyi biokhimichnyi zhurnal 78(2): 62–72.
  • Brown, K. D., Lataxes, T. A., Shangary, S., Mannino, J. L., Giardina, J. F., Chen, J., Baskaran, R. (2000). Ionizing radiation exposure results in up-regulation of Ku70 via a p53/ataxia-telangiectasia-mutated protein-dependent mechanism. The Journal of Biological Chemistry 275(9): 6651–6656.
  • Burroughs, S. K., Kaluz, S., Wang, D., Wang, K., Van Meir, E. G., Wang, B. (2013). Hypoxia inducible factor pathway inhibitors as anticancer therapeutics. Future Medicinal Chemistry 5(5): 553–572. http://doi.org/10.4155/fmc.13.17
  • Calzada, M. J., del Peso, L. (2007). Hypoxia-inducible factors and cancer. Clinical & Translational Oncology: Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 9(5): 278–289.
  • Cavadas, M. A. S., Mesnieres, M., Crifo, B., Manresa, M. C., Selfridge, A. C., Scholz, C. C., Taylor, C. T. (2015). REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia, Scientific Reports 5: 17851. http://dx.doi.org/10.1038/srep17851
  • Dukel, M., Streitfeld, W. S., Tang, T. C. C., Backman, L. R. F., Ai, L., May, W. S., Brown, K. D. (2016). The Breast Cancer Tumor Suppressor TRIM29 Is Expressed via ATM-dependent Signaling in Response to Hypoxia. The Journal of Biological Chemistry 291(41): 21541–21552. http://doi.org/10.1074/jbc.M116.730960
  • Hamidian, A., von Stedingk, K., Munksgaard Thoren, M., Mohlin, S., Pahlman, S. (2015). Differential regulation of HIF-1alpha and HIF-2alpha in neuroblastoma: Estrogen-related receptor alpha (ERRalpha) regulates HIF2A transcription and correlates to poor outcome. Biochemical and Biophysical Research Communications 461(3): 560–567.
  • Hu, C.-J., Wang, L.-Y., Chodosh, L. A., Keith, B., Simon, M. C. (2003). Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation. Molecular and Cellular Biology 23(24): 9361–9374. http://doi.org/10.1128/MCB.23.24.9361-9374.2003
  • Jemal, A., Bray, F., Center, M.M., Ferlay, J., Ward, E., Forman, D. (2011). Global Cancer Statistics. American Cancer Society 61: 69-90.
  • Ke, Q., Costa, M. (2006). Hypoxia-inducible factor-1 (HIF-1). Molecular Pharmacology 70(5): 1469–1480. http://doi.org/10.1124/mol.106.027029
  • Keith, B., Johnson, R. S., Simon, M. C. (2011). HIF1α and HIF2α: sibling rivalry in hypoxic tumor growth and progression. Nature Reviews. Cancer 12(1): 9–22. http://doi.org/10.1038/nrc3183
  • Li, Q. F., Wang, X. R., Yang, Y. W., Lin, H. (2006). Hypoxia upregulates hypoxia inducible factor (HIF)-3alpha expression in lung epithelial cells: characterization and comparison with HIF-1alpha. Cell Research 16(6): 548–558. http://doi.org/10.1038/sj.cr.7310072
  • Li, N., Wang, H. X., Qin, C., Wang, X. H., & Han, F. Y. (2015). Relationship between clinicopathological features and HIF-2alpha in gastric adenocarcinoma. Genetics and Molecular Research 14(1): 1404–1413. http://doi.org/10.4238/2015.
  • Liu, Y.-M., Ying, S.-P., Huang, Y.-R., Pan, Y., Chen, W.-J., Ni, L.-Q., Liang, Y. (2016). Expression of HIF-1α and HIF-2α correlates to biological and clinical significance in papillary thyroid carcinoma. World Journal of Surgical Oncology 14: 30. http://doi.org/10.1186/s12957-016-0785-9).
  • Özmen, V. (2009). Breast Cancer in the World and Turkey. J. Breast Health 4: 7-12.
  • Sandlund, J., Ljungberg, B., Wikstrom, P., Grankvist, K., Lindh, G., Rasmuson, T. (2009). Hypoxia-inducible factor-2alpha mRNA expression in human renal cell carcinoma. Acta Oncologica 48(6): 909–914. http://doi.org/10.1080/02841860902824891
  • Semenza, G. L. (2003). Targeting HIF-1 for cancer therapy. Nature Reviews. Cancer 3(10): 721–732. http://doi.org/10.1038/nrc1187
  • Shah, T., Krishnamachary, B., Wildes, F., Mironchik, Y., Kakkad, S. M., Jacob, D., Artemov, D., Bhujwalla, Z. M. (2015). HIF isoforms have divergent effects on invasion, metastasis, metabolism and formation of lipid droplets. Oncotarget 6(29): 28104–28119.
  • Uchida, T., Rossignol, F., Matthay, M. A., Mounier, R., Couette, S., Clottes, E., Clerici, C. (2004). Prolonged hypoxia differentially regulates hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha expression in lung epithelial cells: implication of natural antisense HIF-1alpha. The Journal of Biological Chemistry 279(15): 14871–14878. http://doi.org/10.1074/jbc.M400461200
  • Vaupel, P., Mayer, A. (2007). Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Reviews 26(2): 225–239. http://doi.org/10.1007/s10555-007-9055-1
  • Wang, J.-G., Yuan, L. (2016). HIF-2alpha/Notch3 pathway mediates CoCl2-induced migration and invasion in human breast cancer MCF-7 cells. Acta physiologica Sinica 68(6): 783–789
  • Zhong, H., De Marzo, A. M., Laughner, E., Lim, M., Hilton, D. A., Zagzag, D., Simons, J. W. (1999). Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Research 59(22): 5830–5835.
Toplam 23 adet kaynakça vardır.

Ayrıntılar

Konular Mühendislik
Bölüm Araştırma Makalesi
Yazarlar

Muzaffer Dükel

Kevin D. Brown

Yayımlanma Tarihi 21 Kasım 2017
Kabul Tarihi 16 Kasım 2017
Yayımlandığı Sayı Yıl 2017

Kaynak Göster

APA Dükel, M., & Brown, K. D. (2017). Meme Kanseri Hücrelerinde Zamana Bağlı HIF-2α İfadesi Değişiminin Analizi. Mehmet Akif Ersoy Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 8(Ek (Suppl.) 1), 245-251. https://doi.org/10.29048/makufebed.336876