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ROCK1 geni Lys222Glu ve Arg1262Gln polimorfizmleri ile meme kanseri arasındaki ilişkinin araştırılması

Yıl 2011, Cilt: 17 Sayı: 2, 77 - 81, 01.03.2011

Öz

Bu çalışmanın amacı, Türk popülasyonunda ROCK1 gen polimorfizmleri ile meme kanserinin metastaz yapma özelliği arasındaki muhtemel ilişkiyi araştırmaktır. Bu araştırmada, ROCK1 geninin G15741A (Lys222Glu) ve G156064A (Arg1262Gln) polimorfizmleri için genotip dağılımlarını ve allel frekansını araştırmak ve bu polimorfizmler ile tümör metastazı arasındaki ilişkiyi ortaya koymak amaçlanmıştır. Bu çalışmada, en az 5 yıl süreyle metastaz gelişmemiş meme kanseri olan hastalar (nonmetastatik grup, n=92), metastaz gelişmiş meme kanserli hastalar (metastatik grup, n=101) ve herhangi bir hastalığı olmayan, kanser geçmişi olmayan, ilaç kullanmayan, sigara içmeyen ve alkol kullanmayan sağlıklı bayan gönüllüler (kontrol grubu, n=128) çalışmaya alındı. Hastalardan ve kontrol grubundan alınan kan örneklerinden DNA izole edildi ve LightCycler cihazıyla PCR yöntemi kullanılarak erime eğrisi analizi yapıldı. ROCK1 geni Lys222Glu ve Arg1262Gln polimorfizmlerinin kontrol grubu ile hasta grupları arasında genotip ve allel frekansları bakımından anlamlı fark gözlenmemiştir (P>0.05). Meme kanserinde ROCK1 gen polimorfizmlerinin rolünü araştıran bu ilk çalışmada, Lys222Glu ve Arg1262Gln polimorfizmlerinin meme kanseri gelişme riski veya metastazı ile ilişkili olmadığı bulunmuştur.

Kaynakça

  • 1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60(5):277-300
  • 2. Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 2007;18(3):581-92
  • 3. Fukata Y, Amano M, Kaibuchi K. Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells. Trends Pharmacol Sci 2001;22(1):32-9
  • 4. Matsui T, Amano M, Yamamoto T, Chihara K, Nakafuku M, Ito M, et al. Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho
  • EMBO J 1996;15(9):2208-16
  • 5. Tanaka T, Nishimura D, Wu RC, Amano M, Iso T, Kedes L, et al. Nuclear Rho kinase, ROCK2, targets p300 acetyltransferase. J Biol Chem 2006;281(22):15320-9
  • 6. Noma K, Oyama N, Liao JK. Physiological role of ROCKs in the cardiovascular system. Am J Physiol 2006;290(3):C661-8
  • 7. Kimura K, Ito M, Amano M, Chihara K, Fukata Y, Nakafuku M, et al. Regulation of myosin phosphatase by Rho and Rhoassociated kinase (Rho-kinase). Science 1996;273(5272):245-8
  • 8. Fukata Y, Oshiro N, Kinoshita N, Kawano Y, Matsuoka Y, Bennett V, et al. Phosphorylation of adducin by Rho-kinase plays a crucial role in cell motility. J Cell Biol 1999;145(2):347-61
  • 9. Takamura M, Sakamoto M, Genda T, Ichida T, Asakura H, Hirohashi S. Inhibition of intrahepatic metastasis of human hepatocellular carcinoma by Rho-associated protein kinase inhibitor Y-27632. Hepatology 2001;33(3):577-81
  • 10. Ying H, Biroc SL, Li WW, Alicke B, Xuan JA, Pagila R, et al
  • Rho kinase inhibitor fasudil inhibits tumor progression in human and rat tumor models. Mol Cancer Ther 2006;5(9):2158-64
  • 11. Itoh K, Yoshioka K, Akedo H, Uehata M, Ishizaki T, Narumiya S. An essential part for Rho-associated kinase in the transcellular invasion of tumor cells. Nat Med 1999;5(2):221-5
  • 12. Ruhi HI. Meme kanserinde farmakogenetik. Türkiye Klinikleri Tıp Bilimleri Derg 2010;30(Ek 1):16-21
  • 13. Kalender ME, Demiryürek S, Oztuzcu S, Kizilyer A, Demiryürek AT, Sevinc A, et al. Association between the Thr431Asn polymorphism of the ROCK2 gene and risk of developing metastases of breast cancer. Oncol Res 2010;18(11-12):583-91
  • 14. Burstein HJ, Haris JR, Morrow M. Malignant tumors of the Breast. In: DeVita VT, Lawrence TS, Rosenberg SA (eds)
  • Cancer Principles and Practice of Oncology. (8th ed)
  • Philadelphia, Lippincott Williams and Wilkins, 2008:1606-54
  • 15. Yoshinaga K, Inoue H, Tanaka F, Mimori K, Utsunomiya T, Mori M. Platelet-derived endothelial cell growth factor mediates Rho-associated coiled-coil domain kinase messenger RNA expression and promotes cell motility. Ann Surg Oncol 2003;10(5):582-7
  • 16. van Nieuw Amerongen GP, Koolwijk P, Versteilen A, van Hinsbergh VW. Involvement of RhoA/Rho kinase signaling in VEGF-induced endothelial cell migration and angiogenesis in vitro. Arterioscler Thromb Vasc Biol 2003;23(2):211-7
  • 17. Yin L, Morishige K, Takahashi T, Hashimoto K, Ogata S, Tsutsumi S, et al. Fasudil inhibits vascular endothelial growth factor-induced angiogenesis in vitro and in vivo. Mol Cancer Ther 2007;6(5):1517-25
  • 18. Fritz G, Brachetti C, Bahlmann F, Schmidt M, Kaina B. Rho GTPases in human breast tumours: expression and mutation analyses and correlation with clinical parameters. Br J Cancer 2002;87(6):635-44
  • 19. Lin M, van Golen KL. Rho-regulatory proteins in breast cancer cell motility and invasion. Breast Cancer Res Treat 2004;84(1):49-60
  • 20. Nakajima M, Hayashi K, Katayama K, Amano Y, Egi Y, Uehata M, et al. Wf-536 prevents tumor metastasis by inhibiting both tumor motility and angiogenic actions. Eur J Pharmacol 2003;459(2-3):113-20
  • 21. Nishimura Y, Itoh K, Yoshioka K, Tokuda K, Himeno M
  • Overexpression of ROCK in human breast cancer cells: evidence that ROCK activity mediates intracellular membrane traffic of lysosomes. Pathol Oncol Res 2003;9(2):83-95
  • 22. Ogawa T, Tashiro H, Miyata Y, Ushitora Y, Fudaba Y, Kobayashi T, et al. Rho-associated kinase inhibitor reduces tumor recurrence after liver transplantation in a rat hepatoma model. Am J Transplant 2007;7(2):347-55
  • 23. Bourguignon LY, Singleton PA, Zhu H, Diedrich F
  • Hyaluronan-mediated CD44 interaction with RhoGEF and Rho kinase promotes Grb2-associated binder-1 phosphorylation and phosphatidylinositol 3-kinase signaling leading to cytokine (macrophage-colony stimulating factor) production and breast tumor progression. J Biol Chem 2003;278(32):29420-34
  • 24. Bourguignon LY, Singleton PA, Diedrich F, Stern R, Gilad E
  • CD44 interaction with Na+-H+ exchanger (NHE1) creates acidic microenvironments leading to hyaluronidase-2 and cathepsin B activation and breast tumor cell invasion. J Biol Chem 2004;279(26):26991-7007
  • 25. Seasholtz TM, Wessel J, Rao F, Rana BK, Khandrika S, Kennedy BP, et al. Rho kinase polymorphism influences blood pressure and systemic vascular resistance in human twins: role of heredity. Hypertension 2006;47(5):937-47
  • 26. Demiryurek AT, Erbagci I, Oztuzcu S, Alasehirli B, Ozkara E, Seker M, et al. Lack of association between the Thr431Asn and Arg83Lys polymorphisms of the ROCK2 gene and diabetic retinopathy. Curr Eye Res 2010;35(12):1128-34
  • 27. Yoshida T, Kato K, Yokoi K, Oguri M, Watanabe S, Metoki N, et al. Association of genetic variants with chronic kidney disease in individuals with different lipid profiles. Int J Mol Med 2009;24(2):233-46.

Investigation of the association between ROCK1 gene Lys222Glu ve Arg1262Gln polymorphisms and breast cancer

Yıl 2011, Cilt: 17 Sayı: 2, 77 - 81, 01.03.2011

Öz

The purpose of this study was to evaluate the possible relationship between breast cancer metastasis and ROCK1 gene polymorphisms in Turkish population. In this study, investigation of genotypic distribution and allele frequency of ROCK1 genes G15741A (Lys222Glu) and G156064A (Arg1262Gln) polymorphisms, and studying the association between these polymorphisms and tumor metastasis were aimed. In the present study, we enrolled patients with breast cancer without metastasis at least 5 years (non-metastatic group, n=92), metastatic breast cancer patients (metastatic group, n= 101), and voluntary healthy women, with no disease and cancer history, no drug usage, no smoking and no alcohol abuse (control group, n=128). DNA was isolated from blood samples of patients and control group, and melting curve analyses were made with PCR method at LightCycler equipment. No significant differences in ROCK1 genes Lys222Glu and Arg1262Gln polymorphisms were observed between the control group and patients in terms of genotype and allele frequencies (P>0.05). In this research, which is the first study to evaluate the role of ROCK1 gene polymorphisms in breast cancer, no associations between the Lys222Glu and Arg1262Gln polymorphisms and risk of developing breast cancer or metastasis have been found.

Kaynakça

  • 1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60(5):277-300
  • 2. Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 2007;18(3):581-92
  • 3. Fukata Y, Amano M, Kaibuchi K. Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells. Trends Pharmacol Sci 2001;22(1):32-9
  • 4. Matsui T, Amano M, Yamamoto T, Chihara K, Nakafuku M, Ito M, et al. Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho
  • EMBO J 1996;15(9):2208-16
  • 5. Tanaka T, Nishimura D, Wu RC, Amano M, Iso T, Kedes L, et al. Nuclear Rho kinase, ROCK2, targets p300 acetyltransferase. J Biol Chem 2006;281(22):15320-9
  • 6. Noma K, Oyama N, Liao JK. Physiological role of ROCKs in the cardiovascular system. Am J Physiol 2006;290(3):C661-8
  • 7. Kimura K, Ito M, Amano M, Chihara K, Fukata Y, Nakafuku M, et al. Regulation of myosin phosphatase by Rho and Rhoassociated kinase (Rho-kinase). Science 1996;273(5272):245-8
  • 8. Fukata Y, Oshiro N, Kinoshita N, Kawano Y, Matsuoka Y, Bennett V, et al. Phosphorylation of adducin by Rho-kinase plays a crucial role in cell motility. J Cell Biol 1999;145(2):347-61
  • 9. Takamura M, Sakamoto M, Genda T, Ichida T, Asakura H, Hirohashi S. Inhibition of intrahepatic metastasis of human hepatocellular carcinoma by Rho-associated protein kinase inhibitor Y-27632. Hepatology 2001;33(3):577-81
  • 10. Ying H, Biroc SL, Li WW, Alicke B, Xuan JA, Pagila R, et al
  • Rho kinase inhibitor fasudil inhibits tumor progression in human and rat tumor models. Mol Cancer Ther 2006;5(9):2158-64
  • 11. Itoh K, Yoshioka K, Akedo H, Uehata M, Ishizaki T, Narumiya S. An essential part for Rho-associated kinase in the transcellular invasion of tumor cells. Nat Med 1999;5(2):221-5
  • 12. Ruhi HI. Meme kanserinde farmakogenetik. Türkiye Klinikleri Tıp Bilimleri Derg 2010;30(Ek 1):16-21
  • 13. Kalender ME, Demiryürek S, Oztuzcu S, Kizilyer A, Demiryürek AT, Sevinc A, et al. Association between the Thr431Asn polymorphism of the ROCK2 gene and risk of developing metastases of breast cancer. Oncol Res 2010;18(11-12):583-91
  • 14. Burstein HJ, Haris JR, Morrow M. Malignant tumors of the Breast. In: DeVita VT, Lawrence TS, Rosenberg SA (eds)
  • Cancer Principles and Practice of Oncology. (8th ed)
  • Philadelphia, Lippincott Williams and Wilkins, 2008:1606-54
  • 15. Yoshinaga K, Inoue H, Tanaka F, Mimori K, Utsunomiya T, Mori M. Platelet-derived endothelial cell growth factor mediates Rho-associated coiled-coil domain kinase messenger RNA expression and promotes cell motility. Ann Surg Oncol 2003;10(5):582-7
  • 16. van Nieuw Amerongen GP, Koolwijk P, Versteilen A, van Hinsbergh VW. Involvement of RhoA/Rho kinase signaling in VEGF-induced endothelial cell migration and angiogenesis in vitro. Arterioscler Thromb Vasc Biol 2003;23(2):211-7
  • 17. Yin L, Morishige K, Takahashi T, Hashimoto K, Ogata S, Tsutsumi S, et al. Fasudil inhibits vascular endothelial growth factor-induced angiogenesis in vitro and in vivo. Mol Cancer Ther 2007;6(5):1517-25
  • 18. Fritz G, Brachetti C, Bahlmann F, Schmidt M, Kaina B. Rho GTPases in human breast tumours: expression and mutation analyses and correlation with clinical parameters. Br J Cancer 2002;87(6):635-44
  • 19. Lin M, van Golen KL. Rho-regulatory proteins in breast cancer cell motility and invasion. Breast Cancer Res Treat 2004;84(1):49-60
  • 20. Nakajima M, Hayashi K, Katayama K, Amano Y, Egi Y, Uehata M, et al. Wf-536 prevents tumor metastasis by inhibiting both tumor motility and angiogenic actions. Eur J Pharmacol 2003;459(2-3):113-20
  • 21. Nishimura Y, Itoh K, Yoshioka K, Tokuda K, Himeno M
  • Overexpression of ROCK in human breast cancer cells: evidence that ROCK activity mediates intracellular membrane traffic of lysosomes. Pathol Oncol Res 2003;9(2):83-95
  • 22. Ogawa T, Tashiro H, Miyata Y, Ushitora Y, Fudaba Y, Kobayashi T, et al. Rho-associated kinase inhibitor reduces tumor recurrence after liver transplantation in a rat hepatoma model. Am J Transplant 2007;7(2):347-55
  • 23. Bourguignon LY, Singleton PA, Zhu H, Diedrich F
  • Hyaluronan-mediated CD44 interaction with RhoGEF and Rho kinase promotes Grb2-associated binder-1 phosphorylation and phosphatidylinositol 3-kinase signaling leading to cytokine (macrophage-colony stimulating factor) production and breast tumor progression. J Biol Chem 2003;278(32):29420-34
  • 24. Bourguignon LY, Singleton PA, Diedrich F, Stern R, Gilad E
  • CD44 interaction with Na+-H+ exchanger (NHE1) creates acidic microenvironments leading to hyaluronidase-2 and cathepsin B activation and breast tumor cell invasion. J Biol Chem 2004;279(26):26991-7007
  • 25. Seasholtz TM, Wessel J, Rao F, Rana BK, Khandrika S, Kennedy BP, et al. Rho kinase polymorphism influences blood pressure and systemic vascular resistance in human twins: role of heredity. Hypertension 2006;47(5):937-47
  • 26. Demiryurek AT, Erbagci I, Oztuzcu S, Alasehirli B, Ozkara E, Seker M, et al. Lack of association between the Thr431Asn and Arg83Lys polymorphisms of the ROCK2 gene and diabetic retinopathy. Curr Eye Res 2010;35(12):1128-34
  • 27. Yoshida T, Kato K, Yokoi K, Oguri M, Watanabe S, Metoki N, et al. Association of genetic variants with chronic kidney disease in individuals with different lipid profiles. Int J Mol Med 2009;24(2):233-46.
Toplam 34 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Makaleler
Yazarlar

Mehmet Emin Kalender Bu kişi benim

Şeniz Demiryürek Bu kişi benim

Serdar Öztuzcu Bu kişi benim

Ayşe Kızılyer Bu kişi benim

Abdullah Tuncay Demiryürek Bu kişi benim

Ozan Balakan Bu kişi benim

Celaletdin Camcı Bu kişi benim

Yayımlanma Tarihi 1 Mart 2011
Yayımlandığı Sayı Yıl 2011 Cilt: 17 Sayı: 2

Kaynak Göster

APA Kalender, M. E., Demiryürek, Ş., Öztuzcu, S., Kızılyer, A., vd. (2011). ROCK1 geni Lys222Glu ve Arg1262Gln polimorfizmleri ile meme kanseri arasındaki ilişkinin araştırılması. Gaziantep Medical Journal, 17(2), 77-81.
AMA Kalender ME, Demiryürek Ş, Öztuzcu S, Kızılyer A, Demiryürek AT, Balakan O, Camcı C. ROCK1 geni Lys222Glu ve Arg1262Gln polimorfizmleri ile meme kanseri arasındaki ilişkinin araştırılması. Gaziantep Medical Journal. Mart 2011;17(2):77-81.
Chicago Kalender, Mehmet Emin, Şeniz Demiryürek, Serdar Öztuzcu, Ayşe Kızılyer, Abdullah Tuncay Demiryürek, Ozan Balakan, ve Celaletdin Camcı. “ROCK1 Geni Lys222Glu Ve Arg1262Gln Polimorfizmleri Ile Meme Kanseri arasındaki ilişkinin araştırılması”. Gaziantep Medical Journal 17, sy. 2 (Mart 2011): 77-81.
EndNote Kalender ME, Demiryürek Ş, Öztuzcu S, Kızılyer A, Demiryürek AT, Balakan O, Camcı C (01 Mart 2011) ROCK1 geni Lys222Glu ve Arg1262Gln polimorfizmleri ile meme kanseri arasındaki ilişkinin araştırılması. Gaziantep Medical Journal 17 2 77–81.
IEEE M. E. Kalender, Ş. Demiryürek, S. Öztuzcu, A. Kızılyer, A. T. Demiryürek, O. Balakan, ve C. Camcı, “ROCK1 geni Lys222Glu ve Arg1262Gln polimorfizmleri ile meme kanseri arasındaki ilişkinin araştırılması”, Gaziantep Medical Journal, c. 17, sy. 2, ss. 77–81, 2011.
ISNAD Kalender, Mehmet Emin vd. “ROCK1 Geni Lys222Glu Ve Arg1262Gln Polimorfizmleri Ile Meme Kanseri arasındaki ilişkinin araştırılması”. Gaziantep Medical Journal 17/2 (Mart 2011), 77-81.
JAMA Kalender ME, Demiryürek Ş, Öztuzcu S, Kızılyer A, Demiryürek AT, Balakan O, Camcı C. ROCK1 geni Lys222Glu ve Arg1262Gln polimorfizmleri ile meme kanseri arasındaki ilişkinin araştırılması. Gaziantep Medical Journal. 2011;17:77–81.
MLA Kalender, Mehmet Emin vd. “ROCK1 Geni Lys222Glu Ve Arg1262Gln Polimorfizmleri Ile Meme Kanseri arasındaki ilişkinin araştırılması”. Gaziantep Medical Journal, c. 17, sy. 2, 2011, ss. 77-81.
Vancouver Kalender ME, Demiryürek Ş, Öztuzcu S, Kızılyer A, Demiryürek AT, Balakan O, Camcı C. ROCK1 geni Lys222Glu ve Arg1262Gln polimorfizmleri ile meme kanseri arasındaki ilişkinin araştırılması. Gaziantep Medical Journal. 2011;17(2):77-81.