Cancer Dormancy and Cell Signaling: Induction of P21(waf1) Initiated by Membrane IgM Engagement Increases Survival of B Lymphoma Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1999 Jul 21

PMID 10411940

Citations 12

Authors

R Marches

R Hsueh

J W UHR

Affiliations

Soon will be listed here.

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.

Citing Articles

HDAC inhibitors stimulate LIFR when it is repressed by hypoxia or PTHrP in breast cancer.

Edwards C, Clements M, Vecchi 3rd L, Johnson J, Johnson R J Bone Oncol. 2021; 31:100407.

PMID: 34934614 PMC: 8661052. DOI: 10.1016/j.jbo.2021.100407.

Epigenetic Silencing of BMP6 by the SIN3A-HDAC1/2 Repressor Complex Drives Melanoma Metastasis via FAM83G/PAWS1.

Min D, Byun J, Lee E, Khan A, Liu C, Loudig O Mol Cancer Res. 2021; 20(2):217-230.

PMID: 34610961 PMC: 9744461. DOI: 10.1158/1541-7786.MCR-21-0289.

The current paradigm and challenges ahead for the dormancy of disseminated tumor cells.

Risson E, Nobre A, Maguer-Satta V, Aguirre-Ghiso J Nat Cancer. 2021; 1(7):672-680.

PMID: 33681821 PMC: 7929485. DOI: 10.1038/s43018-020-0088-5.

Beyond Tumor Suppression: Senescence in Cancer Stemness and Tumor Dormancy.

Triana-Martinez F, Loza M, Dominguez E Cells. 2020; 9(2).

PMID: 32028565 PMC: 7072600. DOI: 10.3390/cells9020346.

Controversies in clinical cancer dormancy.

Uhr J, Pantel K Proc Natl Acad Sci U S A. 2011; 108(30):12396-400.

PMID: 21746894 PMC: 3145712. DOI: 10.1073/pnas.1106613108.

References

Demidem A, Lam T, Alas S, Hariharan K, Hanna N, Bonavida B . Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs. Cancer Biother Radiopharm. 1997; 12(3):177-86. DOI: 10.1089/cbr.1997.12.177. View

Taji H, Kagami Y, Okada Y, Andou M, Nishi Y, Saito H . Growth inhibition of CD20-positive B lymphoma cell lines by IDEC-C2B8 anti-CD20 monoclonal antibody. Jpn J Cancer Res. 1998; 89(7):748-56. PMC: 5921892. DOI: 10.1111/j.1349-7006.1998.tb03280.x. View

Hudziak R, Lewis G, Winget M, Fendly B, Shepard H, Ullrich A . p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor. Mol Cell Biol. 1989; 9(3):1165-72. PMC: 362707. DOI: 10.1128/mcb.9.3.1165-1172.1989. View

Page D, DeFranco A . 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; 10(6):3003-12. PMC: 360664. DOI: 10.1128/mcb.10.6.3003-3012.1990. View

Levy R, Miller R . Therapy of lymphoma directed at idiotypes. J Natl Cancer Inst Monogr. 1990; (10):61-8. View

Hasbold J, Klaus G . Anti-immunoglobulin antibodies induce apoptosis in immature B cell lymphomas. Eur J Immunol. 1990; 20(8):1685-90. DOI: 10.1002/eji.1830200810. View

UHR J, Tucker T, May R, Siu H, Vitetta E . Cancer dormancy: studies of the murine BCL1 lymphoma. Cancer Res. 1991; 51(18 Suppl):5045s-5053s. View

Beckwith M, Urba W, Ferris D, Freter C, Kuhns D, Moratz C . 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; 147(7):2411-8. View

Carter P, Presta L, Gorman C, Ridgway J, Henner D, Wong W . Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci U S A. 1992; 89(10):4285-9. PMC: 49066. DOI: 10.1073/pnas.89.10.4285. View

10.

Picker L, Treer J, Collins P, Buck D, Terstappen L . 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; 150(3):1105-21. View

11.

Yefenof E, Picker L, Scheuermann R, Tucker T, Vitetta E, UHR J . Cancer dormancy: isolation and characterization of dormant lymphoma cells. Proc Natl Acad Sci U S A. 1993; 90(5):1829-33. PMC: 45973. DOI: 10.1073/pnas.90.5.1829. View

12.

Hsu F, Kwak L, Campbell M, Liles T, Czerwinski D, Hart S . Clinical trials of idiotype-specific vaccine in B-cell lymphomas. Ann N Y Acad Sci. 1993; 690:385-7. DOI: 10.1111/j.1749-6632.1993.tb44039.x. View

13.

Xiong Y, Hannon G, Zhang H, Casso D, Kobayashi R, Beach D . p21 is a universal inhibitor of cyclin kinases. Nature. 1993; 366(6456):701-4. DOI: 10.1038/366701a0. View

14.

Nishioka W, Welsh R . Susceptibility to cytotoxic T lymphocyte-induced apoptosis is a function of the proliferative status of the target. J Exp Med. 1994; 179(2):769-74. PMC: 2191380. DOI: 10.1084/jem.179.2.769. View

15.

Canman C, Gilmer T, Coutts S, Kastan M . Growth factor modulation of p53-mediated growth arrest versus apoptosis. Genes Dev. 1995; 9(5):600-11. DOI: 10.1101/gad.9.5.600. View

16.

Racila E, Scheuermann R, Picker L, Yefenof E, Tucker T, Chang W . 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; 181(4):1539-50. PMC: 2191969. DOI: 10.1084/jem.181.4.1539. View

17.

Joseph L, Ezhevsky S, Scott D . 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; 6(1):51-7. View

18.

Deng C, Zhang P, Harper J, Elledge S, Leder P . Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control. Cell. 1995; 82(4):675-84. DOI: 10.1016/0092-8674(95)90039-x. View

19.

Meikrantz W, Schlegel R . Apoptosis and the cell cycle. J Cell Biochem. 1995; 58(2):160-74. DOI: 10.1002/jcb.240580205. View

20.

Waldman T, Kinzler K, Vogelstein B . p21 is necessary for the p53-mediated G1 arrest in human cancer cells. Cancer Res. 1995; 55(22):5187-90. View