TITLE:
Impact of the -216G/T Polymorphism on the Sp1 and Epidermal Growth Factor Receptor Interaction in Non-Small Cell Lung Carcinoma
AUTHORS:
A. Mesli-Mostafa, A. Kacimi, B. Merad, N. Belblidia, T. Sahraoui, F.-Z. El Kebir
KEYWORDS:
NSCLC, EGFR, -216G/T, Sp1, -191C/A
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.7 No.7,
July
7,
2016
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.