Connexin43 induced breast tumor cell re-differentiation in three-dimensional cultures
Bibliographic record
Abstract
1460 Normal human mammary epithelium expresses gap junction proteins Cx43 and Cx26, however, gap junctions are frequently down-regulated in breast tumors. We have previously shown that the human breast tumor cell line MDA-MB-231 expresses low levels of endogenous Cx43 and exhibits sparse gap junctional intercellular communication (GJIC). Over-expression of Cx43 by retroviral infection in these cells resulted in little rescue of GJIC with the majority of the connexin being prematurely routed to lysosomes (Qin et al., 2003, JBC 278, 30005). Although there was no effect of connexin over-expression on 2D cell growth, when these cells were implanted into nude mice a dramatic suppression of tumor growth was observed with no apparent increase in gap junctions (Qin et al., 2002, JBC, 277, 29132). Furthermore, when these cells were cultured in soft-agar, colony formation was significantly inhibited in Cx43 or Cx26 over-expressing cells. In more recent studies, when grown in 3D matrigel, control MDA-MB-231 cells formed undifferentiated stellate structures, indicative of a malignancy. In contrast, cells over-expressing Cx43 exhibited growth control and formed more spherical structures indicative of cell re-differentiation. We hypothesize that the effect of Cx43 over-expression on cell growth in 2D versus 3D is due to extracellular matrix signaling. Immunolocalization studies consistently revealed that most of Cx43 did not traffic to the membrane to form junctional complexes signifying that the mechanism for 3D growth control may be GJIC-independent or required little increase in GJIC. To examine the possible signaling pathways regulated by connexin expression in 3D cultures, we extracted RNA from 3D cultures of control and Cx43 over-expressing cells and subjected these preparations to bias gene arrays against human extracellular matrix and adhesion molecules. Currently we are identifying and verifying the genes regulated by Cx43 expression that trigger signal transduction pathway(s) important in mammary epithelial cell differentiation in 3D. Supported by a Canadian Breast Cancer Research Alliance (DWL) and a NSERC (EM).
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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) | 0.001 | 0.001 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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".