Connexin26 Regulates the Expression of Angiogenesis-Related Genes in Human Breast Tumor Cells by Both GJIC-Dependent and -Independent Mechanisms
Bibliographic record
Abstract
We previously reported that over-expression of connexins in mammary tumor cells retarded tumor growth in vivo in the absence of appreciable gap junction formation, highlighting a possible connexin-linked, but gap junctional intercellular communication (GJIC)-independent mechanism. In the current study, we engineered GJIC-deficient MDA-MB-435 human breast tumor cells to express a chimeric Cx26 where the green fluorescent protein was fused to the amino-terminal of Cx26 (GFP-Cx26). Characterization of this chimeric protein revealed that GFP-Cx26 assembled into non-functional gap junction-like clusters that were impermeable to Lucifer Yellow. In contrast, expression of wild-type Cx26 or Cx26 tagged at the carboxy terminal with yellow fluorescent protein, efficiently rescued GJIC in these tumor cells. Interestingly, by screening 96 tumor-related genes, we observed that the expression of Cx26 or GFP-Cx26 in the tumor cells up-regulated both the transcription and the translation of thrombospondin-1 (TSP-1), an anti-angiogenic molecule. Affymetrix array analysis extended the list of Cx26 or GFP-Cx26 regulated genes by ten candidates including connective tissue growth factor (CTGF), another angiogenesis-related gene. CTGF mRNA and protein levels were found to be down-regulated by both Cx26 and GFP-Cx26. Thus, our data indicates that Cx26 regulates angiogenesis-related molecules by mechanisms that are both GJIC-dependent and -independent.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".