ArticleOncotarget2011
Disruption of p16 and activation of Kras in pancreas increase ductal adenocarcinoma formation and metastasis in vivo.
Article in Oncotarget, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 100 citations in OpenAlex.
- Inactivation of CDKN2AARF Promotes p53-Independent Remodeling of the PDAC Tumor Microenvironment.Cancer research · 2026Article
- Acinar-specific loss of activating transcription factor 3 restricts KRASCell death discovery · 2025Article
- Wild-type RAS signaling is an essential therapeutic target inScience signaling · 2025Article
- ARID1A mutation drives gastric tumorigenesis via activating type 2 immune dominant microenvironment.iScience · 2025Article
- Unlocking the Genetic Secrets of Pancreatic Cancer:Cancers · 2025Review
- Review
- Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer.Current issues in molecular biology · 2024Review
- Identification and analysis of pancreatic intraepithelial neoplasia: opportunities and challenges.Frontiers in endocrinology · 2024Review
- Hematopoietic progenitor kinase 1 inhibits the development and progression of pancreatic intraepithelial neoplasia.The Journal of clinical investigation · 2023Article
- Pancreatic cancer: Advances and challenges.Cell · 2023Review
- Oxylipin-PPARγ-initiated adipocyte senescence propagates secondary senescence in the bone marrow.Cell metabolism · 2023Article
- Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications.Journal of hematology & oncology · 2023Review
- Inactivation ofCancer research communications · 2022Article
- Review
- Bmi1 suppresses protein synthesis and promotes proteostasis in hematopoietic stem cells.Genes & development · 2022Article
- Article
- Exploiting senescence for the treatment of cancer.Nature reviews. Cancer · 2022Review
- Article
- Loss of the wild-type KRAS allele promotes pancreatic cancer progression through functional activation of YAP1.Oncogene · 2021Article
- Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Inactivation of tumor suppressor gene p16/INK4A and oncogenic activation of KRAS occur in almost all pancreatic cancers. To better understand the roles of p16 in pancreatic tumorigenesis, we created a conditional p16 knockout mouse line (p16flox/flox), in which p16 is specifically disrupted in a tissue-specific manner without affecting p19/ARF expression. p16flox/flox; LSL-KrasG12D; Pdx1-Cre mice developed the full spectrum of pancreatic intraepithelial neoplasia (mPanIN) lesions, pancreatic ductal adenocarcinoma (PDA), and metastases were observed in all the mice. Here we report a mouse model that simulates human pancreatic tumorigenesis at both genetic and histologic levels and is ideal for studies of metastasis. During the progression from primary tumors to metastases, the wild-type allele of Kras was progressively lost (loss of heterozygosity at Kras or LOH at Kras) in p16flox/flox; LSL- KrasG12D; Pdx1-Cre mice. These observations suggest a role for Kras beyond tumor initiation. In vitro assays performed with cancer cell lines derived from primary pancreatic tumors of these mice showed that cancer cells with LOH at Kras exhibited more aggressive phenotypes than those retained the wild-type Kras allele, indicating that LOH at Kras can provide cancer cells functional growth advantages and promote metastasis. Increased LOH at KRAS was also observed in progression of human pancreatic primary tumors to metastases, again supporting a role for the KRAS gene in cancer metastasis. This finding has potential translational implications- future KRAS target therapies may need to consider targeting oncogenic KRAS specifically without inhibiting wild-type KRAS function.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.