ERK4, a new tumor suppressor gene candidate implicated in prostate cancer progression
Bibliographic record
Abstract
In Canada, prostate cancer is the most frequently diagnosed cancer in man and the third leading cause of cancer related death. In order to identify genes implicated in prostate cancer progression, we used microcell-mediated chromosome transfer to introduce chromosomes 10, 12, 17 and 18 into human PC-3-derived cells lines called PC-3M-Pro4GP1 and PC-3M-LN4GP2. The properties of the hybrids were determined by invasion assay, growth in soft agar and injection into nude mice (either subcutaneously or orthotopically). After the transfer of chromosome 18 in our cell lines, we have identified two sets of hybrids that show opposite phenotypes. Genotyping studies indicated that one locus on chromosome 18 (D18S51) contains an additional allele in the less tumorigenic hybrids. This allele is absent in the highly tumorigenic hybrids as well as in tumors derived from the injection of less tumorigenic cells into nude mice. Preliminary microarray data analysis showed that two genes located in the D18S51 region (ERK4 and BCL2) were differentially expressed in the less tumorigenic hybrids compared to the tumorigenic hybrids. We examined publicly available microarray data sets and found that ERK4 was down regulated in prostate, adrenal and lung cancers. We have also examined the possibility that the metastasis suppressor gene MASPIN (also located in the D18S51 region) could be responsible for the less tumorigenic phenotype seen in our hybrids. Real-time PCR studies showed that ERK4 and MASPIN were up regulated in the less tumorigenic hybrids and that BCL2 was down regulated in these same cells. However, Western immunoblot experiments did not show any difference in the MASPIN or the BCL2 protein levels. Thus, MASPIN or a BCL2 repressor are most likely not responsible for the less tumorigenic phenotype of our hybrids. Interestingly, re-introduction of ERK4 in our tumorigenic hybrids completely abolished their ability to form colonies in soft agar and to invade through Matrigel. However, there is no difference in tumor growth rate upon injection of ERK4-over-expressing cells compared to mock-transfected controls. We also found a non-synonymous polymorphism in the coding sequence of the ERK4 gene. This polymorphism is present at the same frequency in Asian, European and Ashkenazi Jewish populations but less frequently in the African (Yoruba) population. This is the first report of a non-synonymous polymorphism in the coding sequence of the ERK4 gene. However, based on a limited number of prostate cancer cases, the presence of this poylmorphism is not associated with the disease. Taken together, these results demonstrate that ERK4 is a good candidate for a tumor suppressor gene implicated in prostate cancer progression.
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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 | 0.001 | 0.001 |
| 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) | 0.002 | 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".