Mapk phosphatase dusp16/mkp-7, a candidate tumor suppressor for chromosome region 12p12–13, reduces bcr-abl-induced transformation

ABSTRACT Recurrent chromosome 12p deletions are associated with distinct tumor types and suggest the presence of a tumor suppressor gene (TSG). Previously, we mapped an EST with similarity

to a protein tyrosine phosphatase to the minimally deleted region for all these neoplasms. The corresponding gene, _DUSP16_/_MKP-7_, was recently shown to code for a mitogen-activated

protein kinase phosphatase, suggestive for a function as tumor suppressor. Overexpression of _DUSP16_ in BCR-ABL-transformed Rat-1 fibroblasts reduces their transforming capacity _in vitro_

and _in vivo_ via downregulation of BCR-ABL-induced JNK activation. A role for DUSP16 as a regulator of JNK signaling was further demonstrated via overexpression in Ba/F3 cells, which

increased their antiapoptosis. However, no inactivating mutations could be detected in leukemia patients hemizygous for _DUSP16_, and the effect of hemizygosity on _DUSP16_ expression level

could not be assessed due to the variability of _DUSP16_ transcript levels observed in leukaemia cell lines and in patients. Taken together, the functional data point to a context-dependent

role for DUSP16 on cell transformation and apoptosis, reflecting the dual role of JNK, and therefore suggest that DUSP16 might be haploinsufficient for tumor suppression. Access through your

institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 50 print

issues and online access $259.00 per year only $5.18 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to

local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT

BEING VIEWED BY OTHERS LOSS OF NOL10 LEADS TO IMPAIRED DISEASE PROGRESSION OF NUP98::DDX10 LEUKEMIA Article 22 April 2025 THE CHROMOSOME 21 KINASE DYRK1A: EMERGING ROLES IN CANCER BIOLOGY

AND POTENTIAL AS A THERAPEUTIC TARGET Article 26 February 2022 INABILITY TO PHOSPHORYLATE Y88 OF P27KIP1 ENFORCES REDUCED P27 PROTEIN LEVELS AND ACCELERATES LEUKEMIA PROGRESSION Article Open

access 21 May 2022 REFERENCES * Antonyak MA, Moscatello DK and Wong AJ . (1998). _J. Biol. Chem._, 273, 2817–2822. * Baens M, Wlodarska I, Corveleyn A, Hoornaert I, Hagemeijer A and Marynen

P . (1999). _Genomics_, 56, 40–50. * Bost F, McKay R, Dean N and Mercola D . (1997). _J. Biol. Chem._, 272, 33422–33429. * Camps M, Nichols A and Arkinstall S . (2000). _FASEB J._, 14,

6–16. * Cools J, Mentens N, Odero MD, Peeters P, Wlodarska I, Delforge M, Hagemeijer A and Marynen P . (2002). _Blood_, 99, 1776–1784. * Cortez D, Reuther G and Pendergast AM . (1997).

_Oncogene_, 15, 2333–2342. * Davis RJ . (2000). _Cell_, 103, 239–252. * Fero ML, Randel E, Gurley KE, Roberts JM and Kemp CJ . (1998). _Nature_, 396, 177–180. * Furukawa T, Yatsuoka T,

Youssef EM, Abe T, Yokoyama T, Fukushige S, Soeda E, Hoshi M, Hayashi Y, Sunamura M, Kobari M and Horii A . (1998). _Cytogenet. Cell Genet._, 82, 156–159. * Guo B, Godzik A and Reed JC .

(2001). _J. Biol. Chem._, 276, 2780–2785. * Hatta Y, Takeuchi S, Yokota J and Koeffler HP . (1997). _Br. J. Cancer_, 75, 1256–1262. * Hetet G, Dastot H, Baens M, Brizard A, Sigaux F,

Grandchamp B and Stern M-H . (2000). _Hematol. J._, 1, 42–47. * Hoshino R, Tanimura S, Watanabe K, Kataoka T and Kohno M . (2001). _J. Biol. Chem._, 276, 2686–2692. * Huang C, Li J, Ma WY

and Dong Z . (1999). _J. Biol. Chem._, 274, 29672–29676. * Kibel AS, Faith DA, Bova GS and Isaacs WB . (2000). _J. Urol._, 164, 192–196. * Kibel AS, Freije D, Isaacs WB and Bova GS . (1999).

_Genes Chromosomes Cancer_, 25, 270–276. * Kibel AS, Schutte M, Kern SE, Isaacs WB and Bova GS . (1998). _Cancer Res._, 58, 5652–5655. * Latil A, Guerard M, Berthon P and Cussenot O .

(2001). _Genes Chromosomes Cancer_, 31, 199–200. * Lewis TS, Shapiro PS and Ahn NG . (1998). _Adv. Cancer Res._, 74, 49–139. * Liu Q and Sommer SS . (1995). _Bio Techniques_, 18, 470–477. *

Lugo TG and Witte ON . (1989). _Mol. Cell. Biol._, 9, 1263–1270. * Masuda K, Shima H, Watanabe M and Kikuchi K . (2001). _J. Biol. Chem._, 276, 39002–39011. * Montpetit A, Boily G and

Sinnett D . (2002). _Eur. J. Hum. Genet._, 10, 62–71. * Muda M, Theodosiou A, Rodrigues N, Boschert U, Camps M, Gillieron C, Davies K, Ashworth A and Arkinstall S . (1996). _J. Biol. Chem._,

271, 27205–27208. * Nesbit MA, Hodges MD, Campbell L, de Meulemeester TM, Alders M, Rodrigues NR, Talbot K, Theodosiou AM, Mannens MA, Nakamura Y, Little PF and Davies KE . (1997).

_Genomics_, 42, 284–294. * Palacios R and Steinmetz M . (1985). _Cell_, 41, 727–734. * Pawlak G and Helfman DM . (2001). _Curr. Opin. Genet. Dev._, 11, 41–47. * Philipp-Staheli J, Payne SR

and Kemp CJ . (2001). _Exp. Cell Res._, 264, 148–168. * Pinson KI, Brennan J, Monkley S, Avery BJ and Skarnes WC . (2000). _Nature_, 407, 535–538. * Raitano AB, Halpern JR, Hambuch TM and

Sawyers CL . (1995). _Proc. Natl. Acad. Sci. USA_, 92, 11746–11750. * Raynaud S, Cave H, Baens M, Bastard C, Cacheux V, Grosgeorge J, Guidal-Giroux C, Guo C, Vilmer E, Marynen P and

Grandchamp B . (1996). _Blood_, 87, 2891–2899. * Romana SP, Le Coniat M, Poirel H, Marynen P, Bernard O and Berger R . (1996). _Leukemia_, 10, 167–170. * Sato Y, Suto Y, Pietenpol J, Golub

TR, Gilliland DG, Davis EM, Le Beau MM, Roberts JM, Vogelstein B, Rowley JD and Bohlander SK . (1995). _Blood_, 86, 1525–1533. * Slingerland J and Pagano M . (2000). _J. Cell. Physiol._,

183, 10–17. * Smith A, Ramos-Morales F, Ashworth A and Collins M . (1997). _Curr. Biol._, 7, 893–896. * Spirin KS, Simpson JF, Takeuchi S, Kawamata N, Miller CW and Koeffler HP . (1996).

_Cancer Res._, 56, 2400–2404. * Stegmaier K, Takeuchi S, Golub TR, Bohlander SK, Bartram CR and Koeffler HP . (1996). _Cancer Res._, 56, 1413–1417. * Takeuchi S, Mori N, Koike M, Slater J,

Park S, Miller CW, Miyoshi I and Koeffler HP . (1996). _Cancer Res._, 56, 738–740. * Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP and He X . (2000).

_Nature_, 407, 530–535. * Tanoue T, Yamamoto T, Maeda R and Nishida E . (2001). _J. Biol. Chem._, 276, 26629–26639. * Wlodarska I, Marynen P, La Starza R, Mecucci C and Van den Berghe H .

(1996). _Cytogenet. Cell Genet._, 72, 229–235. * Xiao L and Lang W . (2000). _Cancer Res._, 60, 400–408. Download references ACKNOWLEDGEMENTS We thank Anne Hagemeijer, Iwona Wlodarska and

Michel Stul for providing us patient material, and Vic Van Duppen for the FACS analysis. This work was supported by Grants G0121.00 and G0368.02 from ‘FWO-Vlaanderen’, Belgium (to PM) and

GOA Research Fund KU Leuven (to JG). Inge Hoornaert is supported by the ‘IWT-Vlaanderen’, Belgium. Mathijs Baens is a ‘Postdoctoraal Onderzoeker’ of the ‘FWO-Vlaanderen’, Belgium. AUTHOR

INFORMATION AUTHORS AND AFFILIATIONS * Department of Human Genetics, Human Genome Laboratory, Flanders Interuniversity Institute for Biotechnology (VIB), Katholieke Universiteit Leuven,

Herestraat 49, Leuven, B-3000, Belgium Inge Hoornaert, Peter Marynen & Mathijs Baens * Department of Molecular Cell Biology, Division of Biochemistry, Katholieke Universiteit Leuven,

Herestraat 49, Leuven, B-3000, Belgium Jozef Goris * Department of Pathology, Katholieke Universiteit Leuven, Herestraat 49, Leuven, B-3000, Belgium Raf Sciot Authors * Inge Hoornaert View

author publications You can also search for this author inPubMed Google Scholar * Peter Marynen View author publications You can also search for this author inPubMed Google Scholar * Jozef

Goris View author publications You can also search for this author inPubMed Google Scholar * Raf Sciot View author publications You can also search for this author inPubMed Google Scholar *

Mathijs Baens View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Mathijs Baens. RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Hoornaert, I., Marynen, P., Goris, J. _et al._ MAPK phosphatase DUSP16/MKP-7, a candidate tumor suppressor for chromosome region 12p12–13,

reduces BCR-ABL-induced transformation. _Oncogene_ 22, 7728–7736 (2003). https://doi.org/10.1038/sj.onc.1207089 Download citation * Received: 16 December 2002 * Revised: 05 August 2003 *

Accepted: 07 August 2003 * Published: 30 October 2003 * Issue Date: 30 October 2003 * DOI: https://doi.org/10.1038/sj.onc.1207089 SHARE THIS ARTICLE Anyone you share the following link with

will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt

content-sharing initiative KEYWORDS * tumor suppressor gene * MAPK phosphatase * chromosome 12p12–13 * transformation