Expression of kruppel-like factor 5 mediates anchorage-independent growth and good prognosis in human lung cancer.
Bibliographic record
Abstract
84 Ras mutations have been identified in human lung adenocarcinoma; however, attempts to clinically target mutant Ras have encountered significant problems. The Ras/Erk pathway is responsible for much of the oncogenicty of the Ras oncoproteins, providing rationale for the analysis of Ras/Erk downstream signaling targets such as the transcription factor Kruppel-like Factor 5 (KLF5). The Ras/Erk pathway mediates the expression of KLF5. KLF5 may facilitate cell entry into the S phase of the cell cycle, and may regulate downstream mediators of Ras function in cell proliferation such as cyclin D1; however, KLF5 may also act in a tumor suppressive manner. We have generated a KLF5 specific antisera, and have determined that KLF5 is expressed in several mouse lung tumor models which stimulate Ras signaling. Moreover, we have applied this reagent to a tissue array of primary human lung cancer biopsies and found that patients with tumors expressing high levels of KLF5 have significantly better prognosis than those without KLF5 expression. To understand the molecular basis of this observation we overexpressed KLF5 in Ras-mutant human lung adenocarcinoma cell lines. In comparison to empty vector controls, growth rates of KLF5 overexpressing cells increased after (but not before) cultures became confluent. In contrast, knockdown of KLF5 expression limited growth. Moreover, soft agar assays showed a significant reduction in colony formation of KLF5 knockdown cells. These findings indicate that the KLF5 transcription factor may mediate anchorage independent growth in human lung cancer cells. Interestingly, anchorage independent growth is one function mutant Ras signaling. Gene expression analyses reveal that the putative KLF5 target gene cyclin D1 is deregulated upon manipulation of KLF5 in human lung adenocarcinoma cell lines. In mice, conditional deletion of Klf5 in the lung dramatically ablates cyclin D1 expression, but only in a subset of cells. These data provide the first validation of a Klf5 target gene in primary lung cells, and the first indication of the prognostic value of KLF5 expression in human lung cancer.
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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 | 0.000 | 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 | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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".