Abstract B43: RECQ1, a breast cancer susceptibility gene, is upregulated by cancer therapeutics in a p53-dependent manner
Bibliographic record
Abstract
Abstract Sensitivity of cancer cells to DNA-damaging chemotherapeutics is determined by DNA repair processes. Consequently, cancer cells may upregulate expression of certain DNA repair genes as a mechanism to promote chemoresistance. Here, we report identification of RECQ1, a breast cancer susceptibility gene that encodes the most abundant RecQ helicase in humans, as a p53-regulated target potentially acting as a defense against DNA-damaging agents. Quantitative RT-PCR analysis in a variety of cancer cell lines revealed RECQ1 to be upregulated following DNA damage, which was confirmed by Western blot experiments. Significant increase in RECQ1 mRNA level was observed following treatment with alkylating agent methylmethanesulfonate (MMS) as well as the representative chemotherapeutic drugs doxorubicin, temozolomide and fotemustine. Upregulation of RECQ1 expression also appeared to depend on the nature of DNA lesion. Induction of RECQ1 by genotoxins requires p53 since it was observed in p53 wild-type but not in p53 null cells. Consistent with that, the RECQ1 promoter is bound by endogenous p53 and is responsive to p53 in luciferase assay. Knocking down RECQ1 expression in cancer cells resulted in increased sensitivity to MMS, fotemustine and temozolomide supporting the hypothesis that RECQ1 is involved in the recovery of cells from DNA damage. Notably, RECQ1 is frequently overexpressed and amplified in a variety of cancers. As RECQ1 efficiently protects cells from genomic instability through repair of DNA lesions including those induced by alkylating and other chemotherapeutic agents, RECQ1 overexpression may provide resistance to anti-cancer drugs. RECQ1 expression level may therefore serve to predict chemotherapeutic response of cancer patients and timely implementation of alternative therapeutic strategies. Citation Format: Xing Lu, Swetha Parvathaneni, Sudha Sharma. RECQ1, a breast cancer susceptibility gene, is upregulated by cancer therapeutics in a p53-dependent manner [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montreal, QC, Canada. Philadelphia (PA): AACR; Mol Cancer Res 2017;15(4_Suppl):Abstract nr B43.
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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 | 0.001 | 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 | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".