NF-kappaB in Pancreatic Cancer

Overview

Journal Int J Gastrointest Cancer

Date 2003 Aug 12

PMID 12909735

Citations 28

Authors

Guido M Sclabas

Shuichi Fujioka

Christian Schmidt

Douglas B Evans

Paul J Chiao

Affiliations

Soon will be listed here.

Abstract

Although the genetic profile of pancreatic cancer is emerging as a result of much research, the role of specific genetic alterations that initiate tumorigenesis and produce its cardinal clinical features of locally aggressive growth, metastasis, and chemotherapy resistance remains unresolved. Recently, a number of studies have shown that the inhibition of constitutive NF-kappaB activation, one of the frequent molecular alterations in pancreatic cancer, inhibits tumorigenesis and metastasis. It also sensitizes pancreatic cancer cell lines to anticancer agent-induced apoptosis. Therefore because of the crucial role of NF-kappaB in pancreatic cancer, it is a potential target for developing novel therapeutic strategies for the disease. In vivo and in vitro models that mimic the tumorigenic phenotypes in the appropriate histological and molecular concert would be very useful for confirming the suspected role of the pancreatic cancer signature genetic lesions and better understanding the molecular basis of this disease.

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References

Takaesu G, Surabhi R, Park K, Ninomiya-Tsuji J, Matsumoto K, Gaynor R . TAK1 is critical for IkappaB kinase-mediated activation of the NF-kappaB pathway. J Mol Biol. 2003; 326(1):105-15. DOI: 10.1016/s0022-2836(02)01404-3. View

JACOBS M, Harrison S . Structure of an IkappaBalpha/NF-kappaB complex. Cell. 1998; 95(6):749-58. DOI: 10.1016/s0092-8674(00)81698-0. View

Schutte M, Hruban R, Geradts J, Maynard R, Hilgers W, Rabindran S . Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res. 1997; 57(15):3126-30. View

Lenardo M, Baltimore D . NF-kappa B: a pleiotropic mediator of inducible and tissue-specific gene control. Cell. 1989; 58(2):227-9. DOI: 10.1016/0092-8674(89)90833-7. View

Wilentz R, Su G, Dai J, Sparks A, Argani P, Sohn T . Immunohistochemical labeling for dpc4 mirrors genetic status in pancreatic adenocarcinomas : a new marker of DPC4 inactivation. Am J Pathol. 2000; 156(1):37-43. PMC: 1868651. DOI: 10.1016/S0002-9440(10)64703-7. View

Yeh P, Chuang S, Yeh K, Song Y, Ea C, Cheng A . Increase of the resistance of human cervical carcinoma cells to cisplatin by inhibition of the MEK to ERK signaling pathway partly via enhancement of anticancer drug-induced NF kappa B activation. Biochem Pharmacol. 2002; 63(8):1423-30. DOI: 10.1016/s0006-2952(02)00908-5. View

Darieva Z, Pospelov V, Pospelova T . [Transcription factor NF-kappa B/RelA are constitutively activated and localized in the cell nuclei of E1A + cHa-Ras transformants]. Tsitologiia. 1999; 41(7):622-7. View

Wang W, Abbruzzese J, Evans D, Larry L, Cleary K, Chiao P . The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. Clin Cancer Res. 1999; 5(1):119-27. View

Woronicz J, Gao X, Cao Z, Rothe M, Goeddel D . IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK. Science. 1997; 278(5339):866-9. DOI: 10.1126/science.278.5339.866. View

10.

Karin M, Ben-Neriah Y . Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol. 2000; 18:621-63. DOI: 10.1146/annurev.immunol.18.1.621. View

11.

Mendelsohn J, Baselga J . The EGF receptor family as targets for cancer therapy. Oncogene. 2001; 19(56):6550-65. DOI: 10.1038/sj.onc.1204082. View

12.

Sumitomo M, Tachibana M, Nakashima J, Murai M, Miyajima A, Kimura F . An essential role for nuclear factor kappa B in preventing TNF-alpha-induced cell death in prostate cancer cells. J Urol. 1999; 161(2):674-9. View

13.

Barkett M, Gilmore T . Control of apoptosis by Rel/NF-kappaB transcription factors. Oncogene. 1999; 18(49):6910-24. DOI: 10.1038/sj.onc.1203238. View

14.

Yang J, Lin Y, Guo Z, Cheng J, Huang J, Deng L . The essential role of MEKK3 in TNF-induced NF-kappaB activation. Nat Immunol. 2001; 2(7):620-4. DOI: 10.1038/89769. View

15.

Sylla B, Temin H . Activation of oncogenicity of the c-rel proto-oncogene. Mol Cell Biol. 1986; 6(12):4709-16. PMC: 367256. DOI: 10.1128/mcb.6.12.4709-4716.1986. View

16.

Dong Q, Sclabas G, Fujioka S, Schmidt C, Peng B, Wu T . The function of multiple IkappaB : NF-kappaB complexes in the resistance of cancer cells to Taxol-induced apoptosis. Oncogene. 2002; 21(42):6510-9. DOI: 10.1038/sj.onc.1205848. View

17.

Sumitomo M, Tachibana M, Ozu C, Asakura H, Murai M, Hayakawa M . Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IkappaBalpha overexpression. Hum Gene Ther. 1999; 10(1):37-47. DOI: 10.1089/10430349950019174. View

18.

Regnier C, Song H, Gao X, Goeddel D, Cao Z, Rothe M . Identification and characterization of an IkappaB kinase. Cell. 1997; 90(2):373-83. DOI: 10.1016/s0092-8674(00)80344-x. View

19.

Xiao G, Harhaj E, Sun S . NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100. Mol Cell. 2001; 7(2):401-9. DOI: 10.1016/s1097-2765(01)00187-3. View

20.

Sen R, Baltimore D . Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell. 1986; 47(6):921-8. DOI: 10.1016/0092-8674(86)90807-x. View