Abstract P4-04-06: Histone H2A Inhibits Breast Cancer Stem Cell Growth
Bibliographic record
Abstract
Abstract Introduction: Recent studies have identified epigenetic abnormalities as the underlying cause of many breast cancers. In particular, the aberrant acetylation of core histones may be a pivotal source of dysregulated expression of both oncogenes and tumour suppressor genes. Histone deacetylase inhibitors are known to restore histone acetylation and to induce cellular differentiation and growth arrest in breast cancer cells and are the object of extensive research for novel anticancer treatments. We hypothesize that acetylated proteins, in particular histone H2A, could also serve as an alternative substrate for histone deacetylase, thereby promoting cellular histone acetylation and arrest of cancer cell growth. Indeed, our previous results indicate that exogenous calf thymus histone H2A penetrates cells and their nuclei, and induces differentiation and senescence in human breast cancer cells. In contrast, human recombinant histone H2A and H2AX, which lack post-translational modifications, fail to yield these results in spite of the fact that human and bovine histone H2A are virtually identical in their amino acid sequences. However, these recombinant molecules were obtained from bacteria, which lack the intracellular machinery that is necessary to generate post-translational modifications. Thus, post-translational histone modifications are pivotal to the inhibition of breast cancer cell proliferation. Objective: We have extended our study to establish if exogenous calf thymus histone H2A could also induce growth arrest of breast cancer stem cells, and subsequently to determine which portion (s) of the histone H2A molecule is responsible for this action, using overlapping synthetic peptides. Materials and Methods: Breast cancer stem cells were incubated with exogenous calf thymus histone H2A and seven synthetic peptides corresponding to overlapping portions of the entire protein and include all of its post-translational modifications. Cellular morphology was observed and viable cells were counted using trypan blue exclusion. Control experiments were performed with normal breast cells, cells from fibrocystic breast tissues, and breast cancer cells that were not significantly enriched in cancer stem cells. Results and Discussion: Histone H2A inhibits breast cancer stem cell growth and increases their adhesion. Stem cells have recently been identified in many malignant tumours, including breast cancer. Since cancer stem cells are thought to be an important source of therapeutic resistance, they provide a novel research focus for alternative treatment strategies. Our results are very encouraging and may lead to the development of new pharmacological molecules targeting epigenetic abnormalities in breast cancer stem cells. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-04-06.
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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) | 0.001 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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.
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".