• 中國(guó)醫(yī)科大學(xué)附屬盛京醫(yī)院乳腺外科（遼寧沈陽(yáng) 110004）;

目的 　總結(jié)鈣離子結(jié)合酪氨酸磷酸化調(diào)解基因的特征及其在腫瘤發(fā)病中的意義。
方法 　通過(guò)復(fù)習(xí)國(guó)內(nèi)外文獻(xiàn)，回顧分析鈣離子結(jié)合酪氨酸磷酸化調(diào)解基因參與調(diào)節(jié)的信號(hào)通路及其在多種腫瘤中的研究現(xiàn)狀。
結(jié)果 　鈣離子結(jié)合酪氨酸磷酸化調(diào)解基因通過(guò)多種機(jī)理誘導(dǎo)細(xì)胞增殖異常，多種腫瘤的發(fā)生與鈣離子結(jié)合酪氨酸磷酸化調(diào)解基因的異常表達(dá)密切相關(guān)。在分布不同的上皮性腫瘤中，鈣離子結(jié)合酪氨酸磷酸化調(diào)解基因參與調(diào)節(jié)的通路相同，作用靶點(diǎn)相似。
結(jié)論 　鈣離子結(jié)合酪氨酸磷酸化調(diào)解基因的進(jìn)一步深入研究有望為闡明腫瘤的發(fā)生、發(fā)展機(jī)理提供新的途徑，并且可以作為早期診斷及輔助治療的重要手段。

引用本文： 李安,何貴金. 鈣離子結(jié)合酪氨酸磷酸化調(diào)解基因的特征及在腫瘤發(fā)病中的意義. 中國(guó)普外基礎(chǔ)與臨床雜志, 2012, 19(6): 679-682. doi: 復(fù)制

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2. Fiedler SE， Sisson JH， Wyatt TA， et al. Loss of ASP but not ROPN1 reduces mammalian ciliary motility [J]. Cytoskeleton (Hoboken)， 2012， 69(1)：22-32.
3. Liu SL， Ni B， Wang XW， et al. FSCB phosphorylation in mouse spermatozoa capacitation [J]. BMB Rep， 2011， 44(8) ：541-546.
4. Shi LX， He YM， Fang L， et al. CABYR RNAi plasmid construction and NF-κB signal transduction pathway [J]. World J Gastroenterol， 2010， 16(39)：4980-4985.
5. Choy E， Hornicek F， Macconaill L， et al. High-throughput genotyping in osteosarcoma identifies multiple mutations in phosphoinositide-3-kinase and other oncogenes [J]. Cancer， 2011 Oct 17. doi：10. 1002/cncr. 26617.[ Epub ahead of print].
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7. Sen B， Mandal A， Wolkowicz MJ， et al. Splicing inmurine CABYR and its genomic structure [J]. Gene， 2003， 310：67-78.
8. Li YF， He W， Kim YH， et al. CABYR isoforms expressed in late steps of spermiogenes is bind with AKAPs and ropporin in mouse sperm fibrous sheath [J]. Reprod Biol Endocrinol， 2010，8：101.
9. Kim YH， Jha KN， Mandal A， et al. Translation and assembly of CABYR coding region B in fibrous sheath and restriction of calcium binding to coding region A [J]. Dev Biol， 2005， 286(1)：46-56.
10. Newell AE， Fiedler SE， Ruan JM， et al. Protein kinase A R Ⅱ-like (R2D2) proteins exhibit differential localization and AKAP interaction [J]. Cell Motil Cytoskeleton， 2008， 65(7)：539-552.
11. Lamport DT. Life behind cell walls：paradigm lost， paradigm regained [J]. Cell Mol Life Sci， 2001， 58(10)：1363-1385.
12. Hsu HC， Lee YL， Cheng TS， et al. Characterization of two non-testis-specific CABYR variants that bind to GSK3beta with a proline-rich extensin-like domain [J]. Biochem Biophy Res Commun， 2005， 329(3)：1108-1117.
13. Howng SL， Hwang CC， Hsu CY， et al. Involvement of the residues of GSKIP， AxinGID， and FRATtide in their binding with GSK3beta to unravel a novel C-terminal scaffold-binding region [J]. Mol Cell Biochem， 2010， 339 (1-2)：23-33.
14. Holmes T， O’Brien TA， Knight R， et al. Glycogen synthase kinase-3beta nhibition preserves hematopoietic stem cell activity and inhibits leukemic cell growth [J]. Stem Cells， 2008， 26(5)：1288-1297.
15. Vaish V， Sanyal SN. Role of sulindac and celecoxib in the regulation of angiogenesis during the early neoplasm of colon： exploring PI3-K/PTEN/Akt pathway to the canonical Wnt/β-catenin signaling [J]. Biomed Pharmacother， 2012 Feb 17. [ Epub ahead of print].
16. Klaus A， Birchmeier W. Wntsignalling and its impact on development and cancer [J]. Nat Rev Cancer， 2008， 8(5)：387-398.
17. Verras M， Sun Z. Roles and regulation of Wnt signaling and betacatenin in prostate cancer [J]. Cancer Lett， 2006， 237(1)： 22-32.
18. Zeng C， Wang R， Li D， et al. A novel GSK-3 beta-C/EBP alphamiR-122-insulin-like growth factor 1 receptor regulatory circuitry in human hepatocellular carcinoma [J]. Hepatology，2010，52(5)：1702-1712.
19. 王怡. RDA 技術(shù)分析病毒性肝硬化、原發(fā)性肝細(xì)胞癌相關(guān)基因的研究 [D]. 北京：軍事醫(yī)學(xué)科學(xué)院野戰(zhàn)輸血研究所， 2004.
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21. Bienz M. Beta-Catenin： a pivot between cell adhesion and Wnt signalling [J]. Curr Biol， 2005， 15(2)：R64-R67.
22. Persad S， Dedhar S. The role of in tegrin-linked kinase (ILK) in cancer progression [J]. Cancer Metastasis Rev， 2003， 22(4)：375-384.
23. Bryja V， Cajánek L， Grahn A， et al. Inhibition of endocytosis blocks Wnt signalling to beta-catenin by promoting dishevelled degradation [J]. Acta Physiol(Oxf)， 2007， 190(1)：55-61.
24. Hoeflich KP， Luo J， Rubie EA， et al. Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation [J]. Nature， 2000， 406(6791)：86-90.
25. Sanchez JF， Sniderhan LF， Williamson AL， et al. Glycogen synthase kinase 3beta-mediated apoptosis of primary cortical astrocytes involves inhibition of nuclear factor kappaB signaling [J]. Mol Cell Biol， 2003， 23(13)：4649-4662.[ 26] Kotliarova S， Pastorino S， Kovell LC， et al. Glycogen synthase kinase-3 inhibition induces glioma cell death through c-MYC，nuclear factor-kappaB， and glucose regulation [J]. Cancer Res，2008， 68(16)：6643-6651.
26. Luo C， Xiao XY， Liu D， et al. CABYR is a novel cancer test is antigen in lung cancer [J]. Clin Cancer Res， 2007， 13(4)：1288-1297.
27. Medunjanin S， Hermani A， De Servi B， et al. Glycogen synthase kinase-3 interacts with and phosphorylates estrogen receptor alpha and is involved in the regulation of receptor activity [J]. J Biol Chem， 2005， 280(38)：33006-33014.
28. Yan D， Avtanski D， Saxena NK， et al. Leptin-induced epithelialmesenchymal transition in breast cancer cells requires β-catenin activation via Akt/GSK3-and MTA1/Wnt1 protein-dependent pathways [J]. J Biol Chem， 2012， 287(11)： 8598-8612.
29. Farago M， Dominguez I， Landesman-Bollag E， et al. Kinaseinactive glycogen synthase kinase 3beta promotes Wnt signaling and mammary tumorigenesis [J]. Caneer Res， 2005， 65(13)：5792-5801.
30. Dong J， Peng J， Zhang H， et al. Role of glycogen synthase kinase 3beta in rapamycin-mediated cell cycle regulation and chemosensitivity[J]. Cancer Res， 2005， 65(5)：1961-1972.
  1. 1. Naaby-Hansen S， Mandal A， Wolkowicz MJ， et al. CABYR， a novel calcium-binding tyrosine phosphorylation-regulated fibrous sheath protein involved in capacitation [J]. Deve Biol， 2002，242(2)：236-254.
  2. 2. Fiedler SE， Sisson JH， Wyatt TA， et al. Loss of ASP but not ROPN1 reduces mammalian ciliary motility [J]. Cytoskeleton (Hoboken)， 2012， 69(1)：22-32.
  3. 3. Liu SL， Ni B， Wang XW， et al. FSCB phosphorylation in mouse spermatozoa capacitation [J]. BMB Rep， 2011， 44(8) ：541-546.
  4. 4. Shi LX， He YM， Fang L， et al. CABYR RNAi plasmid construction and NF-κB signal transduction pathway [J]. World J Gastroenterol， 2010， 16(39)：4980-4985.
  5. 5. Choy E， Hornicek F， Macconaill L， et al. High-throughput genotyping in osteosarcoma identifies multiple mutations in phosphoinositide-3-kinase and other oncogenes [J]. Cancer， 2011 Oct 17. doi：10. 1002/cncr. 26617.[ Epub ahead of print].
  6. 6. Chiriva-Internati M， Cobos E， Da Silva DM， et al. Sperm fibrous sheath proteins：a potential new class of target antigens for use in human therapeutic cancer vaccines [J]. Cancer Immun，2008， 8：8.
  7. 7. Sen B， Mandal A， Wolkowicz MJ， et al. Splicing inmurine CABYR and its genomic structure [J]. Gene， 2003， 310：67-78.
  8. 8. Li YF， He W， Kim YH， et al. CABYR isoforms expressed in late steps of spermiogenes is bind with AKAPs and ropporin in mouse sperm fibrous sheath [J]. Reprod Biol Endocrinol， 2010，8：101.
  9. 9. Kim YH， Jha KN， Mandal A， et al. Translation and assembly of CABYR coding region B in fibrous sheath and restriction of calcium binding to coding region A [J]. Dev Biol， 2005， 286(1)：46-56.
  10. 10. Newell AE， Fiedler SE， Ruan JM， et al. Protein kinase A R Ⅱ-like (R2D2) proteins exhibit differential localization and AKAP interaction [J]. Cell Motil Cytoskeleton， 2008， 65(7)：539-552.
  11. 11. Lamport DT. Life behind cell walls：paradigm lost， paradigm regained [J]. Cell Mol Life Sci， 2001， 58(10)：1363-1385.
  12. 12. Hsu HC， Lee YL， Cheng TS， et al. Characterization of two non-testis-specific CABYR variants that bind to GSK3beta with a proline-rich extensin-like domain [J]. Biochem Biophy Res Commun， 2005， 329(3)：1108-1117.
  13. 13. Howng SL， Hwang CC， Hsu CY， et al. Involvement of the residues of GSKIP， AxinGID， and FRATtide in their binding with GSK3beta to unravel a novel C-terminal scaffold-binding region [J]. Mol Cell Biochem， 2010， 339 (1-2)：23-33.
  14. 14. Holmes T， O’Brien TA， Knight R， et al. Glycogen synthase kinase-3beta nhibition preserves hematopoietic stem cell activity and inhibits leukemic cell growth [J]. Stem Cells， 2008， 26(5)：1288-1297.
  15. 15. Vaish V， Sanyal SN. Role of sulindac and celecoxib in the regulation of angiogenesis during the early neoplasm of colon： exploring PI3-K/PTEN/Akt pathway to the canonical Wnt/β-catenin signaling [J]. Biomed Pharmacother， 2012 Feb 17. [ Epub ahead of print].
  16. 16. Klaus A， Birchmeier W. Wntsignalling and its impact on development and cancer [J]. Nat Rev Cancer， 2008， 8(5)：387-398.
  17. 17. Verras M， Sun Z. Roles and regulation of Wnt signaling and betacatenin in prostate cancer [J]. Cancer Lett， 2006， 237(1)： 22-32.
  18. 18. Zeng C， Wang R， Li D， et al. A novel GSK-3 beta-C/EBP alphamiR-122-insulin-like growth factor 1 receptor regulatory circuitry in human hepatocellular carcinoma [J]. Hepatology，2010，52(5)：1702-1712.
  19. 19. 王怡. RDA 技術(shù)分析病毒性肝硬化、原發(fā)性肝細(xì)胞癌相關(guān)基因的研究 [D]. 北京：軍事醫(yī)學(xué)科學(xué)院野戰(zhàn)輸血研究所， 2004.
  20. 20. Fuchs BC， Fujii T， Dorfman JD， et al. Epithelial-to-mesenchymal transition and integrin-linked kinase mediate sensitivity to epidermal growth factor receptor inhibition in human hepatoma cells [J]. Cancer Res， 2008， 68(7)：2391-2399.
  21. 21. Bienz M. Beta-Catenin： a pivot between cell adhesion and Wnt signalling [J]. Curr Biol， 2005， 15(2)：R64-R67.
  22. 22. Persad S， Dedhar S. The role of in tegrin-linked kinase (ILK) in cancer progression [J]. Cancer Metastasis Rev， 2003， 22(4)：375-384.
  23. 23. Bryja V， Cajánek L， Grahn A， et al. Inhibition of endocytosis blocks Wnt signalling to beta-catenin by promoting dishevelled degradation [J]. Acta Physiol(Oxf)， 2007， 190(1)：55-61.
  24. 24. Hoeflich KP， Luo J， Rubie EA， et al. Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation [J]. Nature， 2000， 406(6791)：86-90.
  25. 25. Sanchez JF， Sniderhan LF， Williamson AL， et al. Glycogen synthase kinase 3beta-mediated apoptosis of primary cortical astrocytes involves inhibition of nuclear factor kappaB signaling [J]. Mol Cell Biol， 2003， 23(13)：4649-4662.[ 26] Kotliarova S， Pastorino S， Kovell LC， et al. Glycogen synthase kinase-3 inhibition induces glioma cell death through c-MYC，nuclear factor-kappaB， and glucose regulation [J]. Cancer Res，2008， 68(16)：6643-6651.
  26. 26. Luo C， Xiao XY， Liu D， et al. CABYR is a novel cancer test is antigen in lung cancer [J]. Clin Cancer Res， 2007， 13(4)：1288-1297.
  27. 27. Medunjanin S， Hermani A， De Servi B， et al. Glycogen synthase kinase-3 interacts with and phosphorylates estrogen receptor alpha and is involved in the regulation of receptor activity [J]. J Biol Chem， 2005， 280(38)：33006-33014.
  28. 28. Yan D， Avtanski D， Saxena NK， et al. Leptin-induced epithelialmesenchymal transition in breast cancer cells requires β-catenin activation via Akt/GSK3-and MTA1/Wnt1 protein-dependent pathways [J]. J Biol Chem， 2012， 287(11)： 8598-8612.
  29. 29. Farago M， Dominguez I， Landesman-Bollag E， et al. Kinaseinactive glycogen synthase kinase 3beta promotes Wnt signaling and mammary tumorigenesis [J]. Caneer Res， 2005， 65(13)：5792-5801.
  30. 30. Dong J， Peng J， Zhang H， et al. Role of glycogen synthase kinase 3beta in rapamycin-mediated cell cycle regulation and chemosensitivity[J]. Cancer Res， 2005， 65(5)：1961-1972.