Involvement of JNK-mediated pathway in EGF-mediated protection against paclitaxel-induced apoptosis in SiHa human cervical cancer cells

B. Liu, M. Fang, Y. Lu, Y. Lu, Gordon Mills, Z. Fan

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

We investigated the signalling pathways by which epidermal growth factor (EGF) modulates paclitaxel-induced apoptosis in SiHa human cervical cancer cells. SiHa cells exposed to paclitaxel underwent apoptosis, which was strongly inhibited by EGF. This inhibition of apoptosis by EGF was not altered by pharmacological blockade of phosphatidylinositol 3′-OH kinase (PI-3K) with the PI-3K specific inhibitor LY294002 or blockade of the mitogen-activated protein kinase (MAPK) kinase (MEK) with the MEK specific inhibitor PD98059, or by transfection of the cells with PI-3K or MEK dominant-negative expression vectors. EGF did not stimutate PI-3K/Akt, MEK/MAPK, or p38 MAPK activity in SiHa cells but did transiently activate the c-Jun NH2-terminal kinase (JNK). Co-exposure of SiHa cells to SB202190 at concentrations that inhibit JNK abolished the protective effect of EGF on SiHa cells against paclitaxel-induced apoptosis. Our findings indicate that the JNK signaling pathway plays an important role in EGF-mediated protection from paclitaxel-induced apoptosis in SiHa cells.

Original languageEnglish (US)
Pages (from-to)303-311
Number of pages9
JournalBritish Journal of Cancer
Volume85
Issue number2
DOIs
StatePublished - Aug 11 2001
Externally publishedYes

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JNK Mitogen-Activated Protein Kinases
Paclitaxel
Epidermal Growth Factor
Uterine Cervical Neoplasms
Mitogen-Activated Protein Kinase Kinases
Apoptosis
Phosphatidylinositol 3-Kinases
p38 Mitogen-Activated Protein Kinases
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Transfection
Pharmacology

Keywords

  • Apoptosis
  • EGF
  • JNK
  • MAPK
  • Paclitaxel
  • PI-3K

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Involvement of JNK-mediated pathway in EGF-mediated protection against paclitaxel-induced apoptosis in SiHa human cervical cancer cells. / Liu, B.; Fang, M.; Lu, Y.; Lu, Y.; Mills, Gordon; Fan, Z.

In: British Journal of Cancer, Vol. 85, No. 2, 11.08.2001, p. 303-311.

Research output: Contribution to journalArticle

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