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HtrA1 Geni ve İşlevleri

Yıl 2015, Cilt: 12 Sayı: 1, 165 - 172, 15.04.2015

Öz

HtrA (High temprature requirement A) gen ailesi gelişme ile ilgili olup, yüksek seviyedeki ifadeleri
organizmanın canlılığının ve gelişmesinin muhafaza edilmesinde önemli bir role sahiptir. HtrA1 geni; bu gen
ailesine ait olup, serin proteaz işlevi olan HtrA1 proteinini kodlar. HtrA serin proteazlar, kemoterapotik
hücre toksisitesini sağlaması yönünden, günümüzde kanser tedavisinde potansiyel hedef olarak
düşünülmektedir. Çeşitli kanserlerde HtrA1 ekspresyon seviyesinin azaldığı ve yüksek seviyede
ekspresyonunun ise in vitro ve in vivo tümör büyümesini engellediği bugüne kadar yapılan birçok çalışma ile
ortaya konmuştur. Ayrıca HtrA1'in çeşitli hastalıklar için yeni bir tedavi hedefi olabileceği de ileri
sürülmektedir. Özellikle katı tümörlerin tedavisinde antitümör ajan olarak yaygın bir şekilde kullanılan
cisplatin ve paclitaxel ile HtrA1 ekspresyon seviyesinin arttığı gözlenmiştir. Günümüze kadar HtrA gen
ailesinin kanserle ilişkisi hakkında yapılmış olan bütün çalışmalarda, HtrA1 geninin tümör baskılayıcı bir
gen olabileceği yönünde fikirler ileri sürülmüştür. Bu çalışmada; HtrA1 geninin biyolojik süreçlerdeki
işlevleri, çeşitli hastalıklarla ilişkileri, özellikle kanser gelişimi ve tedavisindeki rolleri ele alındı. 

Kaynakça

  • 1) Zumbrunn J, Trueb B. Primary structure of a putative serine protease specific for IGF-binding proteins. FEBS Lett. 1996;398 :187–92. 2) Gray CW, Ward RV, Karran E, Turconi S, Rowles A, Viglienghi D et al. Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response. Eur J Biochem 2000; 267:5699–710. 3) Nie GY, Hampton A, LI Y, Fındlay JK, Salamonsen LA. Identification and cloning of two isoforms of human high-temperature requirement factor A3 (HtrA3), characterization of its genomic structure and comparison of its tissue distribution with HtrA1 and HtrA2. Biochem. J 2003; 371: 39-48. 4)Wang L, Cheong ML, Lee YS, Lee MT, Chena H. High-Temperature Requirement Protein A4 (HtrA4) Suppresses the Fusogenic Activity of Syncytin-1 and Promotes Trophoblast Invasion. Molecular and Cellular Biology 2012; 32 ( 18): 3707–17. 5) Inagaki A, Nishizawa H, Ota S, Suzuki M, Inuzuka H, Miyamura H et al. Upregulation of HtrA4 in the placentas of patients with severe pre-eclampsia. Placenta 2012; 33: 919-26. 6) http://ncbi.nlm.nih.gov/gene/HtrA1 Erişim tarihi: 05.07.2012 7) http://www.genecards.org/ccibin/carddisp.pl.gene Erişim tarihi:05.7.2012. 8) Clausen T, Southan C, Ehrmann M. The HtrAFamily of Proteases: Implications for Protein Composition and Cell Fate. Molecular Cell 2002;Vol. 10, 443–55. 9) Canfield AE, Hadfield KD, Rock CF, Wylie EC, Wilkinson FL. HtrA1: a novel regulator of physiological and pathological matrix mineralization? Biochem Soc Trans 2007;35(P4):669-71. 10) Lipinska B, Sharma S, Georgopoulos C. Sequence analysis and regulation of the HtrA gene of Escherichia coli: a sigma 32-independent mechanism of heatinducible transcription. Nucleic Acids Res 1988; 16:10053–67. 11) Strauch KL, Beckwith J. An escherichia coli mutation preventing degradation of abnormal periplasmic proteins. Proc Natl Acad Sci USA1988;85:1576–80. 12) Chien J, Campioni M, Shridhar V, Baldi A. HtrAserine proteases as potential therapeutic targets in cancer. Curr Cancer Drug Targets 2009;9(4):451-68. 13) Tong Y, Liao J, Zhang Y, Zhou J, Zhang H, Mao M. LOC387715/HTRA1 gene polymorphisms and susceptibility to agerelated macular degeneration: A HuGE review and meta-analysis. Molecular Vision 2010; 16:1958-81. 14) Bakay M, Zhao P, Chen J, Hoffman EP. A webaccessible complete transcriptosome of normal human and DMD muscle. Neuromusc Disord 2002;12:125–41. 15) Zurawa-Janicka D, Skorko-Glonek J, Lipinska B. HtrA proteins as targets in therapy of cancer and other diseases. Expert Opin Ther Targets 2010; 14(7):665-79. 16) Chien J, Aletti G, Baldi A, Catalano V, Muretto P, Keeney GL et al. Serine protease HtrA1 modulates chemotherapy-induced cytotoxicity. J Clin Invest 2006; 116:1994–2004. 17) Doherty M, Boot-Handford RP, Grant ME, Canfield AE. Biochem. Soc. Trans 1998; 26: 410. 18) Hu SI, Carozza M, Klein M, Nantermet P, Luk D, Crowl RM. Human HtrA, an evolutionarily conserved serine protease identified as a differentially expressed gene product in osteoarthritic cartilage. J Biol Chem 1998; 273:34406–12. 19) Luca AD, Falco MD, Severino A, Campioni M, Santini D, Baldi F et al. Distribution of the Serine Protease HtrA1 in Normal Human Tissues. The J Histochem Cytochem 2003;51(10): 1279–84. 20) Nagata T, Takahashi Y, Ishii Y, Asai S, Sugahara M, Nishida Yet al. Profiling of genes differentially expressed between fetal liver and postnatal liver using high-density oligonucleotide DNA array. Int J Mol Med 2003;11:713–21. 21) Luca AD, Falco MD, Luca LD, Penta R, Shridhar V, Baldi F et al. Pattern of Expression of HtrA1 during Mouse development. J Histochem Cytochem 2004; 52(12):1609- 17. 22) Nie G, Li Y, Salamonsen LA. Serine protease HtrA1 is developmentally regulated in trophoblast and uterine decidual cells during placental formation in the mouse. Dev Dyn 2005; 233:1102–09. 23) Nie GY, Hale K, Li Y, Manuelpillai U, Wallace EM, Salamonsen LA. Distinct Expression and Localization of Serine Protease HtrA1 in Human Endometrium and FirstTrimester Placenta. Dev Dyn 2006; 235:3448–55. 24) Tsuchiya A, Yano M, Tocharus J, Kojima H, Fukumoto M, Kawaichi Met al. Expression of mouse HtrA1 serine protease in normal bone and cartilage and its upregulation in joint cartilage damaged by experimental arthritis. Bone 2005; 37: 323–36. 25) Grau S, Richards PJ, Kerr B, Hughes C, Caterson B, Williams AS et al. The role of human HtrA1 in arthritic disease. J. Biol. Chem 2006; 281: 6124–9. 26) Oka C, Tsujimoto R, Kajikawa M, Koshiba-Takeuchi K, Ina J, Yano M et al. Development 2004;131: 1041–53. 27) Launay S, Maubert E, Lebeurrier N, Tennstaedt A, Campioni M, Docagne F et al. HtrA1-dependent proteolysis of TGF-beta controls both neuronal maturation and developmental survival. Cell Death Differ 2008; 15: 1408–16. 28) Hadfield KD, Rock CF, Inkson CA, Dallas SL, Sudre L, Wallis GA, Boot-Handford RP, Canfield AE. HtrA1 Inhibits Mineral Deposition by Osteoblasts. Requirement for the protease and domains. J Biol Chem 2008; 283(9): 5928–38. 29) Hara K, Shiga, A, Fukutake T, Nozaki H, Miyashita A, Yokoseki A et al. Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease. N. Engl. J. Med. 2009;360: 1729–39. 30) ShigaA, Nozaki H, YokosekiA, Nihonmatsu M, Kawata H, Kato T et al. Cerebral small-vessel disease protein HTRA1 controls the amount of TGF-β1 via cleavage of proTGF-β1. Hum Mol Gen 2011;1:20 (9):1800-10. 31) Zhang L, Lam Lim S, Du H, Zhang M, Kozak I, Hannum G, et al. High Temperature Requirement Factor A1 (HTRA1) gene regulates angiogenesis through Transforming Growth Factor-β Family member Growth Differentiation Factor 6. J Biol Chem 2012; 287: 2: 1520–26. 32) Friedman DS, O'Colmain BJ, Muñoz B, Tomany SC, McCarty C ,de Jong PT et al. Prevalence of age-related macular degeneration in the United States. Arch. Ophthalmol. 2004;122: 564–72. 33)Yoshida T, DeWan D, Zhang H, Sakamoto R, Okamoto H, Minami M, et al. HTRA1 promoter polymorphism predisposes Japanese to agerelated macular degeneration. Mol Vis 2007; 13: 545-8. 34) Balasubbu S, Sundaresan P, Rajendran A, Ramasamy K, Govindarajan G, Perumalsamy N et al. Association analysis of nine candidate gene polymorphisms in Indian patients with type 2 diabetic retinopathy. BMC Med Genet 2010;11:158. 35) Grau S, Baldi A, Bussani R, Tian X, Stefanescu R, Przybylski M, et al. Implications of the serine protease HtrA1 in amyloid precursor protein processing. Proc. Natl. Acad. Sci. USA2005 ;102: 6021–6. 36) Clawson AG, Bui V, Xin P, Wang N, Pan W. Intracellular Localization of the Tumor Suppressor HtrA1/Prss11 and its Association With HPV16 E6 and E7 Proteins. J Cell Biochem 2008;105 :81–8. 37) Chien J, Ota T, Aletti G, Shridhar R, Boccellino M, Quagliuolo L, et al. Serine Protease HtA1 Associates with Microtubules and Inhibits Cell Migration. Mol Cell Biol 2009;29(15):4177–87. 38) Chien J, Staub J, Hu S, Erickson-Johnson MR, Couch FJ, Smith DI, et al. Acandidate tumor suppressor HtrA1 is downregulated in ovarian cancer. Oncogene 2004;23:1636–44. 39) Shridhar V, Sen A, Chien J, Staub J, Avula R, Kovats S, et al. Identification of underexpressed genes in earlyand late-stage primary ovarian tumors by suppression subtraction hybridization. Cancer Res. 2002; 62:262–70. 40) Baldi A, Luca AD, Morini M, Battista T, Felsani A, Baldi F, et al. The HtrA1 serine protease is downregulated during human melanoma progression and repress growth of metastatic melanoma cells. Oncogene 2002; 221: 6684–8. 41) Bowden MA, Lisa A. Cossens DN, Jobling T, Salamonsen LA, Nie G. Serine proteases HTRA1 and HTRA3 are down regulated with increasing grades of human endometrial cancer. Gynecologic Oncology 2006;103:253–60. 42) Narkiewics J, Lapinska-Szumczyk S, ZurawaJD, SkorkoGJ, Emerich J, Lipinska B. Expression ofhuman HtrA1, HtrA2, HtrA3 and TGF-ß1 genes in primary endometrial cancer. Oncology Reports 2009; 21: 1529- 37. 43) Mullany SA, Moslemi-Kebria M, Rattan R, Khurana A, Clayton A, Ota T, et al. Expression and functional significance of HtrA1 loss in endometrial cancer. Clin Cancer Res 2011;17(3):427-36. 44) Narkiewicz J, Klasa MD, ZurawaJD, SkorkoGJ, Emerich J, Lipinska B. Changes in mRNA and protein levels of human HtrA1, HtrA2 and HtrA3 in ovarian cancer. Clinical Biochemistry 2008;41 561–69. 45) He X, Ota T, Liu P, Su C, Chien J, Shridhar V. Downregulation of HtrA1 promotes resistance to anoikis and peritoneal dissemination of ovarian cancer cells. Cancer Res 2010;70(8): 3109-18. 46) Zurawa JD, Kobiela J, Stefaniak T, Wozniak A, Narkiewicz J, Wozniak M, et al. Changes in expression of serine proteases HtrA1 and HtrA2 during estrogeninduced oxidative stress and nephrocarcinogenesis in male Syrian hamster. Acta Biochimica Polonica. 2008;55(1):9-19. 47) Baldi A, Mottolese M, Vincenzi B, Campioni M, Mellone P, Marino MD, et al. The serine protease HtrA1 is a novel prognostic factor for human mesothelioma. Pharmacogenomics 2008; 9(8):1069-77. 48) Zhu F, Jin L, Luo TP, Luo GH, Tan Y, Qin XH. Serine protease HtrA1 expression in human hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2010; 9(5): 508- 12. 49) Esposito V, Campioni M, Luca AD, Spugnini EP, Baldi F, Cassandro R, et al. Analysis of HtrA1 Serine Protease Expression in Human Lung Cancer. Anticancer Res 2006; 26: 3455-60. 50) Marzioni D, Quaranta A, Lorenzi T, Morroni M, Crescimanno C, Nictolis MD, et al. Expression pattern alterations of the serine protease HtrA1 in normal human placental tissues and in gestational trophoblastic, diseases. Histol Histopathol 2009; 24:1213-22. 51) Youtao Y, Wenlong S, Yi H, Jingyan Z, Hao S, Zhi-hua Z. HtrA1 expression associated with the occurrence and development of esophageal cancer. World Journal of Surgical Oncology 2012; 10:179. 52) Lorenzi T, Lorenzi M, Altobelli E, Marzioni D, Mens E, Quaranta A, at al. HtrA1 in human urothelial bladder cancer: A secreted protein and a potential novel biomarker. Int. J. Cancer 2013;133(11):2650-61. 53) Lehner A, Magdolen V, Schuster T, Kotzsch M, Kiechle M, Meindl A, et al. Downregulation of Serine Protease HTRA1 Is Associated with Poor Survival in Breast Cancer. Plos One 2013; 8 (4), e60359. 54) Akkafa F. Meme Kanserlerinde HtrAGen Ailesinin Gen İfade Seviyelerinin İncelenmesi ve HtrA Proteinlerinin Arşiv Materyallerinde İmmünohistokimyasal Olarak tespit Edilmesi. Doktora Tezi:2012. 55) He X, Khurana A, Maguire JL, Chien J, Shridhar V. HtrA1 sensitizes ovarian cancer cells to cisplatin-induced cytotoxicity by targeting XIAP for degradation. International Journal of Cancer 2011; 130(5):1029-35. 56) Catalano V, Mellone P, d'Avino A, Shridhar V, Staccioli MP, Graziano F, et al. HtrA1, a potential predictor of response to cisplatin-based combination chemotherapy in gastric cancer. Histopathology 2011; 58: 669–678.

HtrA1 Gene and Functions

Yıl 2015, Cilt: 12 Sayı: 1, 165 - 172, 15.04.2015

Öz

HtrAgene family (High temperature requirement A) is related to development and its high expression levels
have an important role in protection of organism's liveliness and development. The gene of HtrA1 which
belongs to the family of HtrA gene codes the HtrA1 protein having serine protease function. HtrA serine
proteases have been considered as potential goal in treatment of cancer in that it provides chemotherapeutic
cell toxicity. It has been revealed by many studies that HtrA1 expression level decreases in some cancer types
and overexpression of HtrA1 inhibits growth of in vitro and in vivo tumor. Also, it has been claimed that
HtrA1 could be a new treatment for several diseases. Especially, the expression of HtrA1 increases with the
use of cisplatin and paclitaxel used commonly as antitumor agent in the treatment of solid tumours. The
results obtained in other HtrA gen family and cancer related studies till this time, it is asserted through the
opinions of researchers that that HtrA1 could be a tumor supressor gene. In this study, functions in
biologycal processes of HtrA1 gene, relationships with various diseases, particularly their role in cancer
development and treatment were discussed.

Kaynakça

  • 1) Zumbrunn J, Trueb B. Primary structure of a putative serine protease specific for IGF-binding proteins. FEBS Lett. 1996;398 :187–92. 2) Gray CW, Ward RV, Karran E, Turconi S, Rowles A, Viglienghi D et al. Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response. Eur J Biochem 2000; 267:5699–710. 3) Nie GY, Hampton A, LI Y, Fındlay JK, Salamonsen LA. Identification and cloning of two isoforms of human high-temperature requirement factor A3 (HtrA3), characterization of its genomic structure and comparison of its tissue distribution with HtrA1 and HtrA2. Biochem. J 2003; 371: 39-48. 4)Wang L, Cheong ML, Lee YS, Lee MT, Chena H. High-Temperature Requirement Protein A4 (HtrA4) Suppresses the Fusogenic Activity of Syncytin-1 and Promotes Trophoblast Invasion. Molecular and Cellular Biology 2012; 32 ( 18): 3707–17. 5) Inagaki A, Nishizawa H, Ota S, Suzuki M, Inuzuka H, Miyamura H et al. Upregulation of HtrA4 in the placentas of patients with severe pre-eclampsia. Placenta 2012; 33: 919-26. 6) http://ncbi.nlm.nih.gov/gene/HtrA1 Erişim tarihi: 05.07.2012 7) http://www.genecards.org/ccibin/carddisp.pl.gene Erişim tarihi:05.7.2012. 8) Clausen T, Southan C, Ehrmann M. The HtrAFamily of Proteases: Implications for Protein Composition and Cell Fate. Molecular Cell 2002;Vol. 10, 443–55. 9) Canfield AE, Hadfield KD, Rock CF, Wylie EC, Wilkinson FL. HtrA1: a novel regulator of physiological and pathological matrix mineralization? Biochem Soc Trans 2007;35(P4):669-71. 10) Lipinska B, Sharma S, Georgopoulos C. Sequence analysis and regulation of the HtrA gene of Escherichia coli: a sigma 32-independent mechanism of heatinducible transcription. Nucleic Acids Res 1988; 16:10053–67. 11) Strauch KL, Beckwith J. An escherichia coli mutation preventing degradation of abnormal periplasmic proteins. Proc Natl Acad Sci USA1988;85:1576–80. 12) Chien J, Campioni M, Shridhar V, Baldi A. HtrAserine proteases as potential therapeutic targets in cancer. Curr Cancer Drug Targets 2009;9(4):451-68. 13) Tong Y, Liao J, Zhang Y, Zhou J, Zhang H, Mao M. LOC387715/HTRA1 gene polymorphisms and susceptibility to agerelated macular degeneration: A HuGE review and meta-analysis. Molecular Vision 2010; 16:1958-81. 14) Bakay M, Zhao P, Chen J, Hoffman EP. A webaccessible complete transcriptosome of normal human and DMD muscle. Neuromusc Disord 2002;12:125–41. 15) Zurawa-Janicka D, Skorko-Glonek J, Lipinska B. HtrA proteins as targets in therapy of cancer and other diseases. Expert Opin Ther Targets 2010; 14(7):665-79. 16) Chien J, Aletti G, Baldi A, Catalano V, Muretto P, Keeney GL et al. Serine protease HtrA1 modulates chemotherapy-induced cytotoxicity. J Clin Invest 2006; 116:1994–2004. 17) Doherty M, Boot-Handford RP, Grant ME, Canfield AE. Biochem. Soc. Trans 1998; 26: 410. 18) Hu SI, Carozza M, Klein M, Nantermet P, Luk D, Crowl RM. Human HtrA, an evolutionarily conserved serine protease identified as a differentially expressed gene product in osteoarthritic cartilage. J Biol Chem 1998; 273:34406–12. 19) Luca AD, Falco MD, Severino A, Campioni M, Santini D, Baldi F et al. Distribution of the Serine Protease HtrA1 in Normal Human Tissues. The J Histochem Cytochem 2003;51(10): 1279–84. 20) Nagata T, Takahashi Y, Ishii Y, Asai S, Sugahara M, Nishida Yet al. Profiling of genes differentially expressed between fetal liver and postnatal liver using high-density oligonucleotide DNA array. Int J Mol Med 2003;11:713–21. 21) Luca AD, Falco MD, Luca LD, Penta R, Shridhar V, Baldi F et al. Pattern of Expression of HtrA1 during Mouse development. J Histochem Cytochem 2004; 52(12):1609- 17. 22) Nie G, Li Y, Salamonsen LA. Serine protease HtrA1 is developmentally regulated in trophoblast and uterine decidual cells during placental formation in the mouse. Dev Dyn 2005; 233:1102–09. 23) Nie GY, Hale K, Li Y, Manuelpillai U, Wallace EM, Salamonsen LA. Distinct Expression and Localization of Serine Protease HtrA1 in Human Endometrium and FirstTrimester Placenta. Dev Dyn 2006; 235:3448–55. 24) Tsuchiya A, Yano M, Tocharus J, Kojima H, Fukumoto M, Kawaichi Met al. Expression of mouse HtrA1 serine protease in normal bone and cartilage and its upregulation in joint cartilage damaged by experimental arthritis. Bone 2005; 37: 323–36. 25) Grau S, Richards PJ, Kerr B, Hughes C, Caterson B, Williams AS et al. The role of human HtrA1 in arthritic disease. J. Biol. Chem 2006; 281: 6124–9. 26) Oka C, Tsujimoto R, Kajikawa M, Koshiba-Takeuchi K, Ina J, Yano M et al. Development 2004;131: 1041–53. 27) Launay S, Maubert E, Lebeurrier N, Tennstaedt A, Campioni M, Docagne F et al. HtrA1-dependent proteolysis of TGF-beta controls both neuronal maturation and developmental survival. Cell Death Differ 2008; 15: 1408–16. 28) Hadfield KD, Rock CF, Inkson CA, Dallas SL, Sudre L, Wallis GA, Boot-Handford RP, Canfield AE. HtrA1 Inhibits Mineral Deposition by Osteoblasts. Requirement for the protease and domains. J Biol Chem 2008; 283(9): 5928–38. 29) Hara K, Shiga, A, Fukutake T, Nozaki H, Miyashita A, Yokoseki A et al. Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease. N. Engl. J. Med. 2009;360: 1729–39. 30) ShigaA, Nozaki H, YokosekiA, Nihonmatsu M, Kawata H, Kato T et al. Cerebral small-vessel disease protein HTRA1 controls the amount of TGF-β1 via cleavage of proTGF-β1. Hum Mol Gen 2011;1:20 (9):1800-10. 31) Zhang L, Lam Lim S, Du H, Zhang M, Kozak I, Hannum G, et al. High Temperature Requirement Factor A1 (HTRA1) gene regulates angiogenesis through Transforming Growth Factor-β Family member Growth Differentiation Factor 6. J Biol Chem 2012; 287: 2: 1520–26. 32) Friedman DS, O'Colmain BJ, Muñoz B, Tomany SC, McCarty C ,de Jong PT et al. Prevalence of age-related macular degeneration in the United States. Arch. Ophthalmol. 2004;122: 564–72. 33)Yoshida T, DeWan D, Zhang H, Sakamoto R, Okamoto H, Minami M, et al. HTRA1 promoter polymorphism predisposes Japanese to agerelated macular degeneration. Mol Vis 2007; 13: 545-8. 34) Balasubbu S, Sundaresan P, Rajendran A, Ramasamy K, Govindarajan G, Perumalsamy N et al. Association analysis of nine candidate gene polymorphisms in Indian patients with type 2 diabetic retinopathy. BMC Med Genet 2010;11:158. 35) Grau S, Baldi A, Bussani R, Tian X, Stefanescu R, Przybylski M, et al. Implications of the serine protease HtrA1 in amyloid precursor protein processing. Proc. Natl. Acad. Sci. USA2005 ;102: 6021–6. 36) Clawson AG, Bui V, Xin P, Wang N, Pan W. Intracellular Localization of the Tumor Suppressor HtrA1/Prss11 and its Association With HPV16 E6 and E7 Proteins. J Cell Biochem 2008;105 :81–8. 37) Chien J, Ota T, Aletti G, Shridhar R, Boccellino M, Quagliuolo L, et al. Serine Protease HtA1 Associates with Microtubules and Inhibits Cell Migration. Mol Cell Biol 2009;29(15):4177–87. 38) Chien J, Staub J, Hu S, Erickson-Johnson MR, Couch FJ, Smith DI, et al. Acandidate tumor suppressor HtrA1 is downregulated in ovarian cancer. Oncogene 2004;23:1636–44. 39) Shridhar V, Sen A, Chien J, Staub J, Avula R, Kovats S, et al. Identification of underexpressed genes in earlyand late-stage primary ovarian tumors by suppression subtraction hybridization. Cancer Res. 2002; 62:262–70. 40) Baldi A, Luca AD, Morini M, Battista T, Felsani A, Baldi F, et al. The HtrA1 serine protease is downregulated during human melanoma progression and repress growth of metastatic melanoma cells. Oncogene 2002; 221: 6684–8. 41) Bowden MA, Lisa A. Cossens DN, Jobling T, Salamonsen LA, Nie G. Serine proteases HTRA1 and HTRA3 are down regulated with increasing grades of human endometrial cancer. Gynecologic Oncology 2006;103:253–60. 42) Narkiewics J, Lapinska-Szumczyk S, ZurawaJD, SkorkoGJ, Emerich J, Lipinska B. Expression ofhuman HtrA1, HtrA2, HtrA3 and TGF-ß1 genes in primary endometrial cancer. Oncology Reports 2009; 21: 1529- 37. 43) Mullany SA, Moslemi-Kebria M, Rattan R, Khurana A, Clayton A, Ota T, et al. Expression and functional significance of HtrA1 loss in endometrial cancer. Clin Cancer Res 2011;17(3):427-36. 44) Narkiewicz J, Klasa MD, ZurawaJD, SkorkoGJ, Emerich J, Lipinska B. Changes in mRNA and protein levels of human HtrA1, HtrA2 and HtrA3 in ovarian cancer. Clinical Biochemistry 2008;41 561–69. 45) He X, Ota T, Liu P, Su C, Chien J, Shridhar V. Downregulation of HtrA1 promotes resistance to anoikis and peritoneal dissemination of ovarian cancer cells. Cancer Res 2010;70(8): 3109-18. 46) Zurawa JD, Kobiela J, Stefaniak T, Wozniak A, Narkiewicz J, Wozniak M, et al. Changes in expression of serine proteases HtrA1 and HtrA2 during estrogeninduced oxidative stress and nephrocarcinogenesis in male Syrian hamster. Acta Biochimica Polonica. 2008;55(1):9-19. 47) Baldi A, Mottolese M, Vincenzi B, Campioni M, Mellone P, Marino MD, et al. The serine protease HtrA1 is a novel prognostic factor for human mesothelioma. Pharmacogenomics 2008; 9(8):1069-77. 48) Zhu F, Jin L, Luo TP, Luo GH, Tan Y, Qin XH. Serine protease HtrA1 expression in human hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2010; 9(5): 508- 12. 49) Esposito V, Campioni M, Luca AD, Spugnini EP, Baldi F, Cassandro R, et al. Analysis of HtrA1 Serine Protease Expression in Human Lung Cancer. Anticancer Res 2006; 26: 3455-60. 50) Marzioni D, Quaranta A, Lorenzi T, Morroni M, Crescimanno C, Nictolis MD, et al. Expression pattern alterations of the serine protease HtrA1 in normal human placental tissues and in gestational trophoblastic, diseases. Histol Histopathol 2009; 24:1213-22. 51) Youtao Y, Wenlong S, Yi H, Jingyan Z, Hao S, Zhi-hua Z. HtrA1 expression associated with the occurrence and development of esophageal cancer. World Journal of Surgical Oncology 2012; 10:179. 52) Lorenzi T, Lorenzi M, Altobelli E, Marzioni D, Mens E, Quaranta A, at al. HtrA1 in human urothelial bladder cancer: A secreted protein and a potential novel biomarker. Int. J. Cancer 2013;133(11):2650-61. 53) Lehner A, Magdolen V, Schuster T, Kotzsch M, Kiechle M, Meindl A, et al. Downregulation of Serine Protease HTRA1 Is Associated with Poor Survival in Breast Cancer. Plos One 2013; 8 (4), e60359. 54) Akkafa F. Meme Kanserlerinde HtrAGen Ailesinin Gen İfade Seviyelerinin İncelenmesi ve HtrA Proteinlerinin Arşiv Materyallerinde İmmünohistokimyasal Olarak tespit Edilmesi. Doktora Tezi:2012. 55) He X, Khurana A, Maguire JL, Chien J, Shridhar V. HtrA1 sensitizes ovarian cancer cells to cisplatin-induced cytotoxicity by targeting XIAP for degradation. International Journal of Cancer 2011; 130(5):1029-35. 56) Catalano V, Mellone P, d'Avino A, Shridhar V, Staccioli MP, Graziano F, et al. HtrA1, a potential predictor of response to cisplatin-based combination chemotherapy in gastric cancer. Histopathology 2011; 58: 669–678.
Toplam 1 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Derleme
Yazarlar

Feridun Akkafa Bu kişi benim

Yayımlanma Tarihi 15 Nisan 2015
Gönderilme Tarihi 30 Aralık 2013
Kabul Tarihi 26 Şubat 2014
Yayımlandığı Sayı Yıl 2015 Cilt: 12 Sayı: 1

Kaynak Göster

Vancouver Akkafa F. HtrA1 Geni ve İşlevleri. Harran Üniversitesi Tıp Fakültesi Dergisi. 2015;12(1):165-72.

Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty