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IGFBP‐2 Expression in MCF‐7 Cells is Regulated by the PI3K/AKT/mTOR Pathway through Sp1 Induced Increase in Transcription

2010· article· en· W2291672711 on OpenAlexaff
Matei Mireuta, Andrew D. Darnel, Michaël Pollak

Bibliographic record

VenueThe FASEB Journal · 2010
Typearticle
Languageen
FieldMedicine
TopicGrowth Hormone and Insulin-like Growth Factors
Canadian institutionsMcGill University Health CentreMcGill University
Fundersnot available
KeywordsPI3K/AKT/mTOR pathwayProtein kinase BTranscription factorChromatin immunoprecipitationRPTORTranscription (linguistics)Molecular biologyBiologySignal transductionChemistryCell biologyCancer researchGene expressionPromoterGeneBiochemistry

Abstract

fetched live from OpenAlex

Insulin‐like growth factor binding protein 2 (IGFBP‐2) has been implicated in the pathophysiology of neoplasia. The PI3K/AKT/mTOR pathway has recently been implicated as a predominant regulator of IGFBP‐2 at the protein level in MCF‐7 breast cancer cells. Objective To elucidate the specific molecular mechanisms that underlie this regulation. Results We show that the PI3K/AKT/mTOR pathway regulates IGFBP‐2 protein levels by modulating IGFBP‐2 mRNA abundance in MCF‐7 cells. This change is achieved by regulating transcription through a critical region present in the first 200 bp upstream of the transcription initiation site where Sp1 transcription factor binds and drives transcription. Manipulations of the PI3K/AKT/mTOR pathway lead to changes in posttranslational modifications and nuclear abundance of Sp1 transcription factor. Methods used QRT‐PCR, ELISA, Western Blot, Luciferase reporter assays, Immunofluorescence, Chromatin immunoprecipitation. Conclusion This work provides a mechanistic explanation for the observed effects of the PI3K/AKT/mTOR pathway on IGFBP‐2 levels in MCF‐7 cells. Matei Mireuta was supported by the graduate studentship from the Weekend to End Breast Cancer of the Jewish General Hospital Foundation.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.001

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.

Opus teacher head0.019
GPT teacher head0.244
Teacher spread0.225 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2010
Admission routes1
Has abstractyes

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