Home LiteratureArticle Details
PMID: 10411940 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cancer dormancy and cell signaling: induction of p21(waf1) initiated by membrane IgM engagement increases survival of B lymphoma cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 15 ·1999-07-20 ·Pages 8711-5

Marches R, Hsueh R, Uhr JW

Abstract

The p21(WAF1) (p21) cyclin-dependent kinase inhibitor plays a major role in regulating cell cycle arrest. It was recently reported that the p53-independent elevation of p21 protein levels is essential in mediating the G(1) arrest resulting from signal transduction events initiated by the crosslinking of membrane IgM on Daudi Burkitt lymphoma cells. Although the role of p21 in cell cycle regulation is well documented, there is little information concerning its role in antibody-mediated apoptosis. In the present study, we examined the involvement of p21 in the regulation of apoptosis by suppressing its induction in anti-IgM-treated Daudi cells through a p21 antisense expression construct approach. Reduction in induced p21 protein levels resulted in diminished G(1) arrest and increased apoptosis. The increased susceptibility to anti-IgM-mediated apoptosis was associated with increased caspase-3-like activity and poly-(ADP)ribose polymerase cleavage. These data suggest that p21 may directly interfere with the caspase cascade, thus playing a dual role in regulating both cell cycle progression and apoptosis.

MeSH Terms
Animals Antibodies/pharmacology Apoptosis/genetics Burkitt Lymphoma Caspase 3 Caspases/metabolism Cell Cycle/genetics Cell Line Cell Survival/genetics Cyclin-Dependent Kinase Inhibitor p21 Cyclins/biosynthesis,genetics DNA, Antisense/genetics G1 Phase/genetics Gene Expression Regulation, Neoplastic Immunoglobulin M/metabolism Mice Poly(ADP-ribose) Polymerases/metabolism Signal Transduction/genetics Transfection
Chemicals
Antibodies Cdkn1a protein, mouse Cyclin-Dependent Kinase Inhibitor p21 Cyclins DNA, Antisense Immunoglobulin M Poly(ADP-ribose) Polymerases Casp3 protein, mouse Caspase 3 Caspases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Marches R
Cancer Immunobiology Center and Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235, USA.
Hsueh R
Uhr J W
References (49)
49 references, click to expand
  1. Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs.
    Cancer Biother Radiopharm. 1997 Jun;12(3):177-86 PMID: 10851464
  2. Growth inhibition of CD20-positive B lymphoma cell lines by IDEC-C2B8 anti-CD20 monoclonal antibody.
    Jpn J Cancer Res. 1998 Jul;89(7):748-56 PMID: 9738982
  3. p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor.
    Mol Cell Biol. 1989 Mar;9(3):1165-72 PMID: 2566907
  4. Antigen receptor-induced cell cycle arrest in WEHI-231 B lymphoma cells depends on the duration of signaling before the G1 phase restriction point.
    Mol Cell Biol. 1990 Jun;10(6):3003-12 PMID: 2342467
  5. Therapy of lymphoma directed at idiotypes.
    J Natl Cancer Inst Monogr. 1990;(10):61-8 PMID: 1693283
  6. Anti-immunoglobulin antibodies induce apoptosis in immature B cell lymphomas.
    Eur J Immunol. 1990 Aug;20(8):1685-90 PMID: 2209683
  7. Cancer dormancy: studies of the murine BCL1 lymphoma.
    Cancer Res. 1991 Sep 15;51(18 Suppl):5045s-5053s PMID: 1884380
  8. Anti-IgM-mediated growth inhibition of a human B lymphoma cell line is independent of phosphatidylinositol turnover and protein kinase C activation and involves tyrosine phosphorylation.
    J Immunol. 1991 Oct 1;147(7):2411-8 PMID: 1918971
  9. Humanization of an anti-p185HER2 antibody for human cancer therapy.
    Proc Natl Acad Sci U S A. 1992 May 15;89(10):4285-9 PMID: 1350088
  10. Control of lymphocyte recirculation in man. I. Differential regulation of the peripheral lymph node homing receptor L-selectin on T cells during the virgin to memory cell transition.
    J Immunol. 1993 Feb 1;150(3):1105-21 PMID: 7678616
  11. Cancer dormancy: isolation and characterization of dormant lymphoma cells.
    Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1829-33 PMID: 8446596
  12. Clinical trials of idiotype-specific vaccine in B-cell lymphomas.
    Ann N Y Acad Sci. 1993 Aug 12;690:385-7 PMID: 8368764
  13. p21 is a universal inhibitor of cyclin kinases.
    Nature. 1993 Dec 16;366(6456):701-4 PMID: 8259214
  14. Susceptibility to cytotoxic T lymphocyte-induced apoptosis is a function of the proliferative status of the target.
    J Exp Med. 1994 Feb 1;179(2):769-74 PMID: 8294885
  15. Growth factor modulation of p53-mediated growth arrest versus apoptosis.
    Genes Dev. 1995 Mar 1;9(5):600-11 PMID: 7698649
  16. Tumor dormancy and cell signaling. II. Antibody as an agonist in inducing dormancy of a B cell lymphoma in SCID mice.
    J Exp Med. 1995 Apr 1;181(4):1539-50 PMID: 7535341
  17. Lymphoma models for B-cell activation and tolerance: anti-immunoglobulin M treatment induces growth arrest by preventing the formation of an active kinase complex which phosphorylates retinoblastoma gene product in G1.
    Cell Growth Differ. 1995 Jan;6(1):51-7 PMID: 7718485
  18. Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control.
    Cell. 1995 Aug 25;82(4):675-84 PMID: 7664346
  19. Apoptosis and the cell cycle.
    J Cell Biochem. 1995 Jun;58(2):160-74 PMID: 7673324
  20. p21 is necessary for the p53-mediated G1 arrest in human cancer cells.
    Cancer Res. 1995 Nov 15;55(22):5187-90 PMID: 7585571
  21. Role of p21 in prostaglandin A2-mediated cellular arrest and death.
    Cancer Res. 1996 Feb 1;56(3):475-9 PMID: 8564956
  22. Repair Defect in p21 WAF1/CIP1 -/- human cancer cells.
    Cancer Res. 1996 May 15;56(10):2250-5 PMID: 8625293
  23. The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells.
    Mol Cell Biol. 1996 Apr;16(4):1335-41 PMID: 8657106
  24. Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21.
    Nature. 1996 Jun 20;381(6584):713-6 PMID: 8649519
  25. Resistance to apoptosis conferred by Cdk inhibitors during myocyte differentiation.
    Science. 1996 Jul 19;273(5273):359-61 PMID: 8662523
  26. Tumour dormancy and cell signalling--III: Role of hypercrosslinking of IgM and CD40 on the induction of cell cycle arrest and apoptosis in B lymphoma cells.
    Ther Immunol. 1995 Jun;2(3):125-36 PMID: 8885131
  27. Protective role of p21(Waf1/Cip1) against prostaglandin A2-mediated apoptosis of human colorectal carcinoma cells.
    Mol Cell Biol. 1996 Dec;16(12):6654-60 PMID: 8943319
  28. Induction of Cip/Kip and Ink4 cyclin dependent kinase inhibitors by interferon-alpha in hematopoietic cell lines.
    Oncogene. 1997 Jan 30;14(4):415-23 PMID: 9053838
  29. p21(Waf1/Cip1) protects against p53-mediated apoptosis of human melanoma cells.
    Oncogene. 1997 Feb 27;14(8):929-35 PMID: 9050992
  30. Up-regulated P21CIP1 expression is part of the regulation quantitatively controlling serum deprivation-induced apoptosis.
    J Cell Biochem. 1997 Mar 1;64(3):434-46 PMID: 9057101
  31. Cell-cycle arrest versus cell death in cancer therapy.
    Nat Med. 1997 Sep;3(9):1034-6 PMID: 9288734
  32. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma.
    Blood. 1997 Sep 15;90(6):2188-95 PMID: 9310469
  33. IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma.
    J Clin Oncol. 1997 Oct;15(10):3266-74 PMID: 9336364
  34. Loss of p21Waf1/Cip1 sensitizes tumors to radiation by an apoptosis-independent mechanism.
    Cancer Res. 1997 Nov 1;57(21):4703-6 PMID: 9354425
  35. Interferon-induces expression of cyclin-dependent kinase-inhibitors p21WAF1 and p27Kip1 that prevent activation of cyclin-dependent kinase by CDK-activating kinase (CAK).
    Oncogene. 1998 Jan 15;16(2):217-25 PMID: 9464540
  36. Apoptosis of malignant human B cells by ligation of CD20 with monoclonal antibodies.
    Blood. 1998 Mar 1;91(5):1644-52 PMID: 9473230
  37. Cancer dormancy: role of cyclin-dependent kinase inhibitors in induction of cell cycle arrest mediated via membrane IgM.
    Cancer Res. 1998 Feb 15;58(4):691-7 PMID: 9485022
  38. Type I interferon induction of the Cdk-inhibitor p21WAF1 is accompanied by ordered G1 arrest, differentiation and apoptosis of the Daudi B-cell line.
    Oncogene. 1998 Apr 9;16(14):1885-90 PMID: 9583686
  39. Feasibility and pharmacokinetic study of a chimeric anti-CD20 monoclonal antibody (IDEC-C2B8, rituximab) in relapsed B-cell lymphoma. The IDEC-C2B8 Study Group.
    Ann Oncol. 1998 May;9(5):527-34 PMID: 9653494
  40. Resistance to Fas-mediated apoptosis: activation of caspase 3 is regulated by cell cycle regulator p21WAF1 and IAP gene family ILP.
    Oncogene. 1998 Aug 27;17(8):931-9 PMID: 9747872
  41. Caspase 3 specifically cleaves p21WAF1/CIP1 in the earlier stage of apoptosis in SK-HEP-1 human hepatoma cells.
    Eur J Biochem. 1998 Oct 1;257(1):242-8 PMID: 9799125
  42. Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells from growth arrest to undergoing apoptosis.
    Oncogene. 1999 Feb 4;18(5):1131-8 PMID: 10022118
  43. Caspase 3 inactivation to suppress Fas-mediated apoptosis: identification of binding domain with p21 and ILP and inactivation machinery by p21.
    Oncogene. 1999 Feb 4;18(5):1239-44 PMID: 10022130
  44. Cleavage of p21Cip1/Waf1 and p27Kip1 mediates apoptosis in endothelial cells through activation of Cdk2: role of a caspase cascade.
    Mol Cell. 1998 Mar;1(4):553-63 PMID: 9660939
  45. Cleavage of CDK inhibitor p21(Cip1/Waf1) by caspases is an early event during DNA damage-induced apoptosis.
    J Biol Chem. 1998 Jul 24;273(30):19207-12 PMID: 9668108
  46. p21-induced cycle arrest in G1 protects cells from apoptosis induced by UV-irradiation or RNA polymerase II blockage.
    Oncogene. 1998 Jul 2;16(26):3461-9 PMID: 9692554
  47. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program.
    J Clin Oncol. 1998 Aug;16(8):2825-33 PMID: 9704735
  48. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study.
    Blood. 1998 Sep 15;92(6):1927-32 PMID: 9731049
  49. Antibodies reactive with the B1 molecule inhibit cell cycle progression but not activation of human B lymphocytes.
    Eur J Immunol. 1986 Aug;16(8):881-7 PMID: 3091375
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.15.8711
Published
1999-07-20
Pages
8711-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC17581
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.96.15.8711 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2