Impact of the -216G/T Polymorphism on the Sp1 and Epidermal Growth Factor Receptor Interaction in Non-Small Cell Lung Carcinoma ()
ABSTRACT
The epidermal growth factor receptor is central to the growth,
differentiation and the mobility of normal and cancer cells. Notably, EGFR
plays an important role in non-small cell lung carcinoma development. Two known
nucleotide variants in EGFR promoter at position -216 (G > T) and -191 (C >
A) are known to influence promoter activity. The transcription factor Sp1
(Specificity protein 1) binds with higher affinity the T allele at position -216
which results in 30% increased transcriptional activity of EGFR. Sequencing of
EGFR promoter region and exon 1 in 18 patients with pulmonary carcinoma
revealed that -216 G/T variant was associated with 58.82% of NSCLC patients
especially those with squamous carcinoma, with predominance of homozygote (T/T)
variants. Strikingly, the -191C/A polymorphism was detected in 11.11% of
patients having a pulmonary carcinoma with the predominance of homozygote (C/C)
variants. The distribution analysis of the four haplotypes (G-C, G-A, T-C and
T-A) and the diplotype (G-C/T-C) of -216G/T and -191C/A polymorphisms, revealed
a clear predominance of T-C haplotype (216T-191C) in squamous cell carcinoma.
The G-C and G-A haplotypes have a lesser distribution while the T-A haplotype
is non-existent. The incidence of (G-C/T-C) diplotype is more important than the
G-A haplotype in all the studied cases. Our results are strongly correlated
with the data of Caucasian population.
Share and Cite:
Mesli-Mostafa, A. , Kacimi, A. , Merad, B. , Belblidia, N. , Sahraoui, T. and Kebir, F. (2016) Impact of the -216G/T Polymorphism on the Sp1 and Epidermal Growth Factor Receptor Interaction in Non-Small Cell Lung Carcinoma.
Journal of Cancer Therapy,
7, 494-499. doi:
10.4236/jct.2016.77052.
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