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Literature DB >> 10098742

Inhibition of transforming growth factor alpha (TGF-alpha)-mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868.

B J Simpson¹, J M Bartlett, K G Macleod, G Rabiasz, E P Miller, A L Rae, P Gordge, R E Leake, W R Miller, J Smyth, S P Langdon.

Abstract

The modulating effects of the epidermal growth factor (EGF) receptor-specific tyrosine kinase inhibitor ZM 252868 on cell growth and signalling have been evaluated in four ovarian carcinoma cell lines PE01, PE04, SKOV-3 and PE01CDDP. Transforming growth factor alpha (TGF-alpha)-stimulated growth was completely inhibited by concentrations > or =0.3 microM in the PE01 and PE04 cell lines and by > or =0.1 microM in SKOV-3 cells. TGF-alpha inhibition of PE01CDDP growth was reversed by concentrations > or =0.1 microM ZM 252868. TGF-alpha-stimulated tyrosine phosphorylation of both the EGF receptor and c-erbB2 receptor in all four cell lines. The inhibitor ZM 252868, at concentrations > or =0.3 microM, completely inhibited TGF-alpha-stimulated tyrosine phosphorylation of the EGF receptor and reduced phosphorylation of the c-erbB2 protein. EGF-activated EGF receptor tyrosine kinase activity was completely inhibited by 3 microM ZM 252868 in PE01, SKOV-3 and PE01CDDP cells. These data indicate that the EGF receptor-targeted TK inhibitor ZM 252868 can inhibit growth of ovarian carcinoma cells in vitro consistent with inhibition of tyrosine phosphorylation at the EGF receptor.

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Year: 1999 PMID： 10098742 PMCID： PMC2362251 DOI： 10.1038/sj.bjc.6690175

Source DB: PubMed Journal: Br J Cancer ISSN： 0007-0920 Impact factor: 7.640

22 in total

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Authors: B J Simpson; S P Langdon; G J Rabiasz; K G Macleod; G L Hirst; J M Bartlett; A J Crew; R A Hawkins; P P Macineira-Perez; J F Smyth; W R Miller
Journal: J Steroid Biochem Mol Biol Date: 1998-02 Impact factor: 4.292

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Journal: Cell Date: 1987-10-23 Impact factor: 41.582

6. Epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer. II. Relationship between receptor expression and response to epidermal growth factor.

Authors: G C Rodriguez; A Berchuck; R S Whitaker; D Schlossman; D L Clarke-Pearson; R C Bast
Journal: Am J Obstet Gynecol Date: 1991-03 Impact factor: 8.661

7. Evidence for the involvement of transforming growth factor alpha and epidermal growth factor receptor autocrine growth mechanism in primary human ovarian cancers in vitro.

Authors: K Morishige; H Kurachi; K Amemiya; Y Fujita; T Yamamoto; A Miyake; O Tanizawa
Journal: Cancer Res Date: 1991-10-01 Impact factor: 12.701

Inhibition of transforming growth factor alpha (TGF-alpha)-mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868.

1. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.

Review 2. Receptors for epidermal growth factor and other polypeptide mitogens.

3. Occurrence of epidermal growth factor receptors in human adnexal tumors and their prognostic value in advanced ovarian carcinomas.

4. Estrogen regulation of transforming growth factor-alpha in ovarian cancer.

5. Point mutation at the ATP binding site of EGF receptor abolishes protein-tyrosine kinase activity and alters cellular routing.

6. Epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer. II. Relationship between receptor expression and response to epidermal growth factor.

7. Evidence for the involvement of transforming growth factor alpha and epidermal growth factor receptor autocrine growth mechanism in primary human ovarian cancers in vitro.

8. Significance of epidermal growth factor receptor in advanced ovarian cancer.

9. Characterization and properties of nine human ovarian adenocarcinoma cell lines.

10. Epidermal growth factor receptors (EGFR) in human ovarian cancer.

Review 1. EGFR/HER-targeted therapeutics in ovarian cancer.

Review 2. Activated epidermal growth factor receptor in ovarian cancer.

3. Targeting the EGF receptor in ovarian cancer with the tyrosine kinase inhibitor ZD 1839 ("Iressa").