Gene Expression Profiling of Adenosine Triphosphate-Binding Cassette Transporters in Response to K-ras Activation and Hypoxia in Human Pancreatic Cancer Cell Cultures
Bibliographic record
Abstract
OBJECTIVES: Pancreatic cancer (PC) is hypoxic and highly resistant to conventional chemotherapy. We sought to determine whether K-ras oncogene and/or hypoxia can induce expression of drug resistance-promoting adenosine triphosphate-binding cassette (ABC) transporters in human PC cell lines. METHODS: Immortalized near-normal human pancreatic ductal epithelial(HPDE) cells, HPDE cells expressing K-rasG12V oncogene, and PCcell lines (MIA PaCa-2, PANC-1, BxPC-3) were subjected to hypoxia and examined for messenger RNA expression of 48 ABC transporters. RESULTS: Mutant K-ras activation and/or hypoxia of HPDE cells led to induction of various ABC transporters. In the case of PC cell lines, no clear correlation was found between expression of constitutively active K-ras and global ABC transporter expression. Moreover, hypoxic treatment of PC cell lines had different effects on ABC transporter expression.Importantly, PC cell lines did not express the multidrug resistance 1 ABC transporter, a major mechanism of drug resistance. However, multi drug resistance 1 expression in the cells was up-regulated in response to continuous exposure to low doses of vincristine, indicating that drug resistance could be induced. CONCLUSIONS: Expression of K-ras oncogene and hypoxia, as well as exposure to drugs, can contribute to drug resistance in PC cells.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 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) | 0.000 | 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".