A Functional Common Polymorphism in a Sp1 Recognition Site of the Epidermal Growth Factor Receptor Gene Promoter
Bibliographic record
Abstract
The epidermal growth factor receptor (EGFR) plays a prominent role in cell growth and development. Its regulation in humans is complex and incompletely understood. In this study, 12 new polymorphisms were discovered in the 5'-regulatory region of EGFR gene and 2 common single nucleotide polymorphisms (-216G/T and -191C/A) were found in the essential promoter area, one of which is located in a Sp1 recognition site (-216). Transient transfection in human cancer and primary cell lines showed significantly different promoter activity between the two most common haplotypes (-216G-191C and -216T-191C). The replacement of G by T at position -216 increases the promoter activity by 30%. A transient transfection assay in the Sp1-deficient cell line (Schneider cell line 2) showed a strong dependence of EGFR promoter activity on Sp1 and confirmed the effect of the aforementioned polymorphisms. Electrophoretic mobility shift assay also showed a significantly higher binding efficiency of nuclear protein or pure Sp1 protein to the T allele compared with the G allele. We then investigated the allelic imbalance of EGFR transcription in fibroblast cell lines with heterozygous genotype at -216G/T but C/C homozygous genotype at -191C/A. The expression of mRNA carrying T-C haplotype was significantly stronger compared with that of G-C haplotype (P < 0.02). Thus, we successfully showed that a common polymorphism in the EGFR promoter was associated with altered promoter activity and gene expression both in vitro and in vivo. Our findings have implications for cancer etiology and therapy and may also be relevant to the inherited susceptibility of other common diseases.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".