Elevated JNK activation contributes to the = pathogenesis of human brain tumors

From: Subject: Elevated JNK activation contributes to the pathogenesis of human brain tumors Date: Sat, 9 Feb 2008 10:38:42 +0100 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01C86B07.F0821860" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.3198 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C86B07.F0821860 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.nature.com/onc/journal/v21/n33/abs/1205593a.html;jsessionid=12DC171B5D7CD28D26FDA1A5A53085DD =EF=BB=BF Elevated JNK activation contributes to the = pathogenesis of human brain tumors

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1=20 August 2002, Volume 21, Number 33, Pages=20 5038-5046

Table=20 of contents Prev= ious Abstract Next= =20 Ful= l=20 text PDF

Original = Paper

Elevated JNK = activation=20 contributes to the pathogenesis of human brain=20 tumors

Marc A Antonyak¹,=20 Lawrence C Kenyon²,=20 Andrew K Godwin³, David=20 C James⁴, = David R=20 Emlet¹, Isamu=20 Okamoto¹, = Mehdi=20 Tnani¹, Marina = Holgado-Madruga¹, David=20 K Moscatello⁵ = and Albert=20 J Wong¹

¹The=20 Kimmel Cancer Institute, Thomas Jefferson = University,=20 Philadelphia, Pennsylvania, PA 19107, = USA

²Department of Pathology, = Anatomy,=20 and Cell Biology, Thomas Jefferson University,=20 Philadelphia, Pennsylvania, PA 19107, = USA

³Department of Medical = Oncology,=20 Fox Chase Cancer Center, Philadelphia, = Pennsylvania, PA=20 19111, USA

⁴Department of Laboratory = Medicine=20 and Pathology, Mayo Clinic and Research = Foundation,=20 Rochester, Minnesota, MN 55905, = USA

⁵Differentiated Cell = Laboratory,=20 Coriell Institute for Medical Research, Camden, = New=20 Jersey, NJ 08103, USA

Correspondence to: A J = Wong, 233 S.=20 10th Street, BLSB 1002, Philadelphia, PA 19107, = USA;=20 E-mail: albert.wong@mail.tju.edu=

Abstract

The ERK pathway is typically associated = with=20 activation of the EGF receptor and has been = shown to=20 play a major role in promoting several tumor = phenotypes.=20 An analogous signaling module, the JNK pathway, = has not=20 been shown to be consistently activated by the = EGF=20 receptor but is instead more uniformly = stimulated by=20 cellular stresses and cytokines. The function of = the JNK=20 pathway in primary tumors is unclear as it has = been=20 implicated in both promoting apoptosis and cell = growth=20 in vitro, which may be a reflection of = the cell=20 lines chosen. Primary human brain tumors = frequently show=20 overexpression of the EGF receptor. To clarify = the role=20 of JNK in tumorigenesis, we have investigated = the role=20 of JNK in a large panel of primary human brain = tumors=20 and tumor derived cell lines. Here we present = evidence=20 that JNK has a major role in promoting = tumorigenesis=20 both in vivo and in vitro. Western = blot=20 analysis demonstrated that 86% (18 of 21) of = primary=20 brain tumors showed evidence of JNK activation = but only=20 38% (8 of 21) showed evidence of ERK activation. = Kinase=20 assays revealed that 77% of brain tumor cell = lines=20 activated JNK in response to EGF (7 of 13) or = had high=20 levels of basal activity (3 of 13), whereas none = of six=20 normal cell lines analysed, including = astrocytes, had=20 these properties. Of several growth factors = examined,=20 EGF produced the highest level of JNK induction = in tumor=20 cell lines and the duration of activation was = greater=20 than that seen for ERK. Expression of a=20 dominant-negative (dn) form of JNK potently = inhibited=20 EGF mediated anchorage independent growth and = protection=20 from cell death in two glial tumor cell lines. = These=20 findings demonstrate that enhanced JNK = activation is=20 frequently found in primary brain tumors and = that this=20 activation contributes to phenotypes related to=20 transformation.

Oncogene (2002) 21, 5038-5046.=20 doi:10.1038/sj.onc.1205593

Keywords

apoptosis; brain tumor; glioblastoma = multiforme; EGF=20 receptor; JNK; MAP kinase

Received 7 August = 2001;=20 revised 5 April 2002; accepted 15 April=20 2002

1 August 2002, Volume 21, Number = 33, Pages=20 5038-5046

Table=20 of contents Prev= ious Abstract Next= =20 Ful= l=20 text PDF


Privacy=20 Policy	=C2=A9=20 2002 Nature Publishing = Group

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