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Imatinib mesylate inhibits Leydig cell tumor growth: evidence for in vitro and in vivo activity
- Source :
- Cancer research. 65(5)
- Publication Year :
- 2005
-
Abstract
- Leydig cell tumors are usually benign tumors of the male gonad. However, if the tumor is malignant, no effective treatments are currently available. Leydig cell tumors express platelet-derived growth factor (PDGF), kit ligand and their respective receptors, PDGFR and c-kit. We therefore evaluated the effects of imatinib mesylate (imatinib), a selective inhibitor of the c-kit and PDGFR tyrosine kinases, on the growth of rodent Leydig tumor cell lines in vivo and in vitro, and examined, in human Leydig cell tumor samples, the expression of activated PDGFR and c-kit and the mutations in exons of the c-kit gene commonly associated with solid tumors. Imatinib caused concentration-dependent decreases in the viability of Leydig tumor cell lines, which coincided with apoptosis and inhibition of proliferation and ligand-stimulated phosphorylation of c-kit and PDGFRs. Mice bearing s.c. allografts of a Leydig tumor cell line treated with imatinib p.o., had an almost complete inhibition of tumor growth, less tumor cell proliferation, increased apoptosis, and a lesser amount of tumor-associated mean vessel density compared with controls. No drug-resistant tumors appeared during imatinib treatment but tumors regrew after drug withdrawal. Human Leydig cell tumors showed an intense expression of the phosphorylated form of c-kit and a less intense expression of phosphorylated PDGFRs. No activating mutations in common regions of mutation of the c-kit gene were found. Our studies suggest that Leydig cell tumors might be a potential target for imatinib therapy.
- Subjects :
- Male
Cancer Research
Receptor, Platelet-Derived Growth Factor alpha
medicine.medical_treatment
Messenger
Apoptosis
Inbred C57BL
Ligands
Piperazines
Rats, Sprague-Dawley
Mice
RNA, Neoplasm
Platelet-Derived Growth Factor
Animals
Receptor, Platelet-Derived Growth Factor beta
Leydig Cell Tumor
Proto-Oncogene Proteins c-kit
Antineoplastic Agents
Humans
Protein-Tyrosine Kinases
Cell Proliferation
Proto-Oncogene Proteins c-sis
Rats
RNA, Messenger
Pyrimidines
Phosphorylation
Mice, Inbred C57BL
Mutation
Settore BIO/16
Leydig cell
Platelet-Derived Growth Factor beta
medicine.anatomical_structure
Oncology
Benzamides
Imatinib Mesylate
Tyrosine kinase
Platelet-derived growth factor receptor
Receptor
medicine.drug
endocrine system
medicine.medical_specialty
Biology
In Vitro Techniques
Internal medicine
medicine
Cell growth
Growth factor
Platelet-Derived Growth Factor alpha
Imatinib
Endocrinology
Imatinib mesylate
Cancer research
biology.protein
RNA
Neoplasm
Sprague-Dawley
Subjects
Details
- ISSN :
- 00085472
- Volume :
- 65
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Cancer research
- Accession number :
- edsair.doi.dedup.....19bebb564e6e817e2e96f97ae31fe53c