Induction of stem cell factor/c-kit/slug signal transduction in multidrug-resistant malignant mesothelioma cells

Alfonso Catalano, Sabrima Rodilossi, Maria Rita Rippo, Paola Caprari, Antonio Procopio

Research output: Contribution to journalArticlepeer-review

Abstract

Malignant mesothelioma (MM) is strongly resistant to conventional chemotherapy by unclear mechanisms. We and others have previously reported that cytokine- and growth factor-mediated signal transduction is involved in the growth and progression of MM. Here, we identified a pathway that involves stem cell factor (SCF)/c-Kit/ Slug in mediating multidrug resistance of MM cells. When we compared gene expression profiles between five MM cells and their multidrug-resistant (MM DX) sublimes, we found that MM DX cells expressed both SCF and c-Kit and had higher mRNA levels of Slug. Knock-down of c-Kit or Slug expression with their respective small interfering RNA sensitized MM DX cells to the induction of apoptosis by different chemotherapeutic agents, including doxorubicin, paclitaxel, and vincristine. Transfection of c-Kit in parental MM cells in the presence of SCF up-regulated Slug and increased resistance to the chemotherapeutic agents. Moreover, MM cells expressing Slug showed a similar increased resistance to the chemotherapeutic agents. These results indicate that induction of Slug by autocrine production of SCF and c-Kit activation plays a key role in conferring a broad spectrum chemoresistance on MM cells and reveal a novel signal transduction pathway for pharmacological or genetic intervention of MM patients.

Original languageEnglish
Pages (from-to)46706-46714
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number45
DOIs
Publication statusPublished - Nov 5 2004

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Induction of stem cell factor/c-kit/slug signal transduction in multidrug-resistant malignant mesothelioma cells'. Together they form a unique fingerprint.

Cite this