expression of GPR54 and KiSS1 in human breast cancer
Bibliographic record
Abstract
4317 Metastatic breast cancer is the second most common cause of death due to cancer in women. Metastin is a 54 amino acid kisspeptide that was characterized as anti-metastatic using in vitro and in vivo studies in a human melanoma cell line. The kisspeptins (Kp10, Kp13, Kp14, and Kp54) are encoded by the KiSS1 gene which is located on chromosome 1q32. The kisspeptin receptor is GPR54 , a G coupled receptor, whose gene is located at chromosome 19p13. Mutated GPR54 is found in humans with hypogonadotropic hypogonadism and GPR54 null mice do not undergo puberty. The kisspeptins stimulate release of LH and FSH through the release of GnRH via the hypothalamo-pituitary axis in mice and humans. As well as having an endocrine function, these genes have also been demonstrated to have an autocrine/paracrine function. Both are expressed in syncytiotrophoblast cells and are thought to control trophoblast invasion during pregnancy. Therefore, metastasis development in breast cancer may in part be determined by GPR54 and KiSS1 expression. Using tissue microarray (TMA) technology, 438 cases of clinical breast cancers with linked outcome data have been assessed for gene copy number of KiSS1 and GPR54 using florescent in situ hybridization (FISH). Using the KiSS1 fluorescent probe, it was discovered that 29/233 breast cancer cases were amplified (12.4%), while only 3 cases showed loss of gene copy number. There was no correlation with survival or ER status. For the GPR54 fluorescent probe, 27/191 cases showed gene loss (14%) while 4 cases were amplified. GPR54 loss correlates with poor survival in node positive patients (p=0.0071). To further assess gene expression, the breast cancer cell lines MDA-MB-231 and MCF-7 were assessed for GPR54 and KiSS1 mRNA levels using real time PCR. Non-metastatic MCF-7 breast cancer cells showed high levels of both GPR54 and KiSS1 expression as compared to the immortalized H-tert breast cell line. Metastatic MDA-MB-231 breast cancer cell line demonstrated increased KiSS1 expression as compared to H-terts but relatively little GPR54 expression as compared to MCF-7 cells or H-tert cells. Western blot analysis confirmed these findings, demonstrating visible GPR54 expression in the MCF-7 protein lysates only. FISH was used on metaphases of MDA-MB-231, MCF-7 and H-tert cells to determine if gene copy number reflected the expression levels. The MDA-MB-231 cells showed three copies of KiSS1 and two to three copies of GPR54 . The MCF-7 cells showed five copies of KiSS1 and two copies of GPR54 , whereas the H-tert cells demonstrated the expected normal two copies of each gene. Loss of GPR54 gene copy number in clinical breast cancer cases of node positive patients and the loss of GPR54 expression in the MDA-MB-231 cell line supports the hypothesis that breast cancer metastasis is in part regulated by GPR54 expression. For the MDA-MB-231 cell line, loss of GPR54 expression may be determined by epigenetic factors.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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) | 0.000 | 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 teacher head, 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".