Detection of overexpressed and phosphorylated wild-type kit receptor in surgical specimens of small cell lung cancer

Elena Tamborini, Lorena Bonadiman, Tiziana Negri, Angela Greco, Samantha Staurengo, Paolo Bidoli, Ugo Pastorino, Marco A. Pierotti, Silvana Pilotti

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: The combinations of various chemotherapeutic drugs currently used to treat advanced small cell lung cancer (SCLC) led to similarly poor survival outcomes, which is why new molecular biology approaches are needed to design and select targeted therapies. Experimental Design: Thirteen stage I SCLC surgical specimens were screened for c-Kit gene mutations by sequencing whole cDNA and for KIT receptor expression/activation by immunoprecipitation and Western blotting. Both the paraffin-embedded and frozen materials were analyzed by immunocytochemistry, and the stem cell factor cognate ligand was assessed by retrotranscription PCR. Results: In all cases, we showed the presence of wild-type KIT receptors by analyzing the entire coding sequence, which together with the detection of the cognate ligand stem cell factor, supports the establishment of an autocrine loop. In addition, the KIT receptor was activated/phosphorylated. The immunoprecipitation/Western blotting data fit the observed immunophenotype. Interestingly, comparison of the level of KIT expression was at least 10 times higher in the tumoral specimens than the normal reference lungs. Conclusions: The KIT molecular profile derived from the analysis of SCLC surgical specimens shows that wild-type KIT is overexpressed and phosphorylated in the presence of stem cell factor. This finding, which is consistent with pathological KIT activation driven by an autocrine loop, is particularly interesting in the light of the recent development of new tyrosine kinase inhibitory drugs, which are highly effective in blocking wild-type KIT receptors.

Original languageEnglish
Pages (from-to)8214-8219
Number of pages6
JournalClinical Cancer Research
Volume10
Issue number24
DOIs
Publication statusPublished - Dec 15 2004

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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