The consequences of insulin-like growth factors/receptors dysfunction in lung cancer.
The aim of this study was to investigate the consequences of insulin-like growth factors (IGF) and IGF receptor dysfunction in lung carcinomas. A correlation between increased expression (at mRNA and protein levels) for IGF-1 and IGF-1R and decreased apoptosis were found in large-cell carcinomas and adenocarcinomas. In 40% of informative adenocarcinomas expressing the highest values of IGF-2 and Ki-67 proteins, M6P/IGF-2R gene had LOH at one allele and a mutation in another allele. All four squamous cell carcinoma samples expressed LOH/mutation in the M6P/IGF-2R gene. The alphaIR3 strongly diminished proliferation and increased apoptosis in cultures established from squamous cell carcinomas overexpressing IGF-2 and IGF-1R. Telomerase activity was assessed in four squamous cell carcinomas. Cell treatment with IGF-1 increased telomerase activity. The opposite was observed when the cells were treated with alphaIR3, which inhibits the activity of IGF-1 receptors. Our findings suggest that disruption of the IGF/IGF receptors axis is involved in lung cancer formation.
Pavelic
Jasminka
J
Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka 54, P. Box 180, HR-10002 Zagreb, Croatia. jpavelic@irb.hr
Krizanac
Simun
S
Kapitanovic
Sanja
S
Pavelic
Ljubomir
L
Samarzija
Miroslav
M
Pavicic
Fadila
F
Spaventi
Sime
S
Jakopovic
Marko
M
Herceg-Ivanovi
Zlata
Z
Pavelic
Kresimir
K
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017451:Receptors, Somatomedin / Q000378:metabolism*; D013002:Somatomedins / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017451:Receptors, Somatomedin; D013002:Somatomedins; D019098:Telomerase