Meme kanserli hastalarda glutatyon s-transferaz izozimlerin çoklu ilaç direnç mekanizmasındaki proteinlerle olan ilişkilerinin incelenmesi
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Tarih
2016
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Yayıncı
Kırıkkale Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Meme kanseri tüm dünyada kadınlarda en çok görülen kanser türlerinin başında gelir. Kanser tedavisinde karşılaşılan klinik sorunlardan birisi de hastalara uygulanan kemoterapiye karşı tümör hücrelerinin geliştirebildikleri dirençtir. Tümör hücrelerinin gösterdiği bu ilaçlara karşı direnç, ilaçların hücre dışına atılmasını sağlayan önemli membran proteinlerinden birisi de ABC (ATP-binding cassette) taşıyıcı proteinleridir. İlaç dirençlilik proteinlerinin yanında diğer hücre içi proteinlerin de etkin olabileceğini bilinmektedir. Bu bağlamda, alkilleyici özellikteki kanser ilaçlarına karşı gelişen dirençte, hücre içi glutatyon ve glutatyon S- konjugat seviyelerindeki artmaşın önemli olduğu bildirilmiştir. Bu çalışmada, meme kanserli hastalar Glutatyon S- transferaz (GST) izozimlerinin çoklu ilaç direnç mekanizmasındaki proteinlerle olan ilişkilerinin incelenmesi amaçlanmıştır. Bu amaçla, Dr. Abdurrahman Yurtaslan Ankara Onkoloji Eğitim ve Araştırma Hastanesi Patoloji Kliniği arşivinden, kemoterapi almamış 95 (Kadın; yaş ortalaması: 60,14±12,86) ve kemoterapi almış 50 (Kadın; yaş ortalaması: 58,41±12,16) meme kanserli parafine gömülü hasta dokusu normal ve tümörlü parafine gömülü dokuları çalışma grubu olarak belirlendi. Tümörlü dokularda MDR-1 (P-gp), MRP-1, MRP-2, MRP-3, MRP-6, MRP-7 ve BXP-34, BRCP-21, GST Alfa-1 (GSTA-1), GST Mü-1 (GSTM1), GST Teta-1 (GSTT1), GST Pi-1 (GSTP1), GST Omega-1 (GSTO1), GST Zeta-1 (GSTZ1), GST Sigma-1 (GSTS1), GST Kappa-1 (GSTK1) protein ifadeleri immunohistokimyasal boyama yöntemiyle belirlendi. İmmunohistokimyasal incelemelerde; kemoterapi almış meme kanserli hastalarda GSTP1, GSTT1, GSTM1, GSTA1, GSTS1, GSTZ1, GSTK1, MRP1, MRP2, MRP3 ve MRP7 protein ifadelerinin tümörlü dokularda normal dokulara oranla daha fazla olduğu görüldü ve istatistiksel olarak anlamlı bulunurken (p<0,05), GSTO1, BXP21 ve BXP34 izozimlerinin istatistiksel olarak anlamlı bulunamadı (p>0,05). Kemoterapi almamış meme kanserli hastalarda ise GSTP1, GSTT1, GSTM1, GSTA1, GSTZ1 ve GSTK1, MRP1, MRP2, MRP3 protein ifadelerinin tümörlü dokularda normal dokulara oranla daha fazla olduğu görüldü ve istatistiksel olarak anlamlı bulunurken (p<0,05), GSTO1 ve GSTS1, MRP7, BXP21 ve BXP34 istatistiksel olarak anlamlı bulunamadı (p>0,05). Ayrıca hem kemoterapi almış hem de kemoterapi almamış hastaların tümörlü dokuların birbirleriyle karşılaştırıldığında ise kemoterapi almış grupta kemoterapi almamış gruba oranla GSTP1,GSTT1 ve MRP3 izozimlerinin protein ifadesi daha yüksek olup istatistiksel olarak anlamlı bulundu (p<0,05). Bu çalışmada, GSTP1 ve GSTT1 izozimlerinin ve MRP-3 kemoterapi direncine neden olabileceği ve meme kanseri oluşumunda rolü olabileceği söyleyebiliriz.
Breast cancer is one the most common cancer types of the women worldwide. In the treatment of cancer, one of the problems encountered in clinical practise is the developmed chemotherapy resistance in the tumor cell. Resistance of tumor cells to these drugs has shown, that helps drugs outside the cell membrane protein is one of the most important members of the ABC ( ATP -binding cassette ) transporter proteins are.Besides that drug resistance protein is known to be effective on other intracellular proteins. In this context, the alkylating functionality at developing resistance to the cancer drug has been reported that intracellular glutathione and glutathione S- conjugates in the role of the increased level. In this study, we aimed to investigate the relationship between the proteins in the Glutathione S- transferase (GST) by patients with breast cancer multidrug resistance mechanism. Forthispurpose, paraffin-embedded normal and cancerous tissues from chemotherapy non-treated 95 ( Woman; age average 60.14 ± 12.86 ) and chemotherapy treated 50 ( Woman; age average 58.41 ± 12.16 ) with breast cancer were used as the study materials were obtained from the Dr. Abdurrahman Yurtaslan Ankara Oncology Education and Research pathology archives. Instudied tumor tissues MDR-1 (P-gp), MRP-1, MRP-2, MRP-3, MRP-6, MRP-7 and BXP-34, BRCP-21, GST Alfa-1 (GSTA-1), GST Mü-1 (GSTM1), GST Teta-1 (GSTT1), GST Pi-1 (GSTP1), GST Omega-1 (GSTO1), GST Zeta-1 (GSTZ1), GST Sigma-1 (GSTS1), GST Kappa-1 (GSTK1) isoenzymes were detected immunohistochemical staining methods. Inimmunohistochemical examinations GSTP1, GSTT1, GSTM1, GSTA1, GSTO1, GSTS1, GSTZ1 ve GSTK1, MRP1, MRP2, MRP3, MRP7, BXP21 expressions were higher in tumor epithelium than those in normal epithelium in chemotherapy-treated breast cancer patients' tissues (p<0,05) and however, there was no statistical difference in GSTO1,BXP21 ve BXP34 isoenzymes expression (p?0.05). The GSTP1, GSTT1, GSTM1, GSTA1, GSTZ1, GSTK1, MRP1, MRP2 and MRP3 expressions were higher in tumor epithelium than that in normal epithelium in non-treated breast cancer patients's tissues (p<0,05) and however, there was no statistical difference inGSTO1 ve GSTS1, MRP7, BXP21 ve BXP34 (p?0.05).GSTP1,GSTT1 and MRP3 expressions were significantly higher in chemotherapy-treated than those in non-treated breast cancer patients' tissues (p<0.05). In this study, it could be said that GSTT1, GSTP1 isozymes and the MRP-3 may play a role in chemotherapy resistance and tumorigenesis of breast cancer.
Breast cancer is one the most common cancer types of the women worldwide. In the treatment of cancer, one of the problems encountered in clinical practise is the developmed chemotherapy resistance in the tumor cell. Resistance of tumor cells to these drugs has shown, that helps drugs outside the cell membrane protein is one of the most important members of the ABC ( ATP -binding cassette ) transporter proteins are.Besides that drug resistance protein is known to be effective on other intracellular proteins. In this context, the alkylating functionality at developing resistance to the cancer drug has been reported that intracellular glutathione and glutathione S- conjugates in the role of the increased level. In this study, we aimed to investigate the relationship between the proteins in the Glutathione S- transferase (GST) by patients with breast cancer multidrug resistance mechanism. Forthispurpose, paraffin-embedded normal and cancerous tissues from chemotherapy non-treated 95 ( Woman; age average 60.14 ± 12.86 ) and chemotherapy treated 50 ( Woman; age average 58.41 ± 12.16 ) with breast cancer were used as the study materials were obtained from the Dr. Abdurrahman Yurtaslan Ankara Oncology Education and Research pathology archives. Instudied tumor tissues MDR-1 (P-gp), MRP-1, MRP-2, MRP-3, MRP-6, MRP-7 and BXP-34, BRCP-21, GST Alfa-1 (GSTA-1), GST Mü-1 (GSTM1), GST Teta-1 (GSTT1), GST Pi-1 (GSTP1), GST Omega-1 (GSTO1), GST Zeta-1 (GSTZ1), GST Sigma-1 (GSTS1), GST Kappa-1 (GSTK1) isoenzymes were detected immunohistochemical staining methods. Inimmunohistochemical examinations GSTP1, GSTT1, GSTM1, GSTA1, GSTO1, GSTS1, GSTZ1 ve GSTK1, MRP1, MRP2, MRP3, MRP7, BXP21 expressions were higher in tumor epithelium than those in normal epithelium in chemotherapy-treated breast cancer patients' tissues (p<0,05) and however, there was no statistical difference in GSTO1,BXP21 ve BXP34 isoenzymes expression (p?0.05). The GSTP1, GSTT1, GSTM1, GSTA1, GSTZ1, GSTK1, MRP1, MRP2 and MRP3 expressions were higher in tumor epithelium than that in normal epithelium in non-treated breast cancer patients's tissues (p<0,05) and however, there was no statistical difference inGSTO1 ve GSTS1, MRP7, BXP21 ve BXP34 (p?0.05).GSTP1,GSTT1 and MRP3 expressions were significantly higher in chemotherapy-treated than those in non-treated breast cancer patients' tissues (p<0.05). In this study, it could be said that GSTT1, GSTP1 isozymes and the MRP-3 may play a role in chemotherapy resistance and tumorigenesis of breast cancer.
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