MAPK signaling is required for dedifferentiation of acinar cells and development of pancreatic intraepithelial neoplasia in mice
Open accessAbstract
Background & aims Kras signaling via mitogen-activated protein kinase (MAPK) is highly up-regulated in pancreatic cancer cells. We investigated whether MAPK signaling is required for the initiation and maintenance of pancreatic carcinogenesis in mice.Methods We studied the formation and maintenance of pancreatic intraepithelial neoplasia (PanINs) in p48Cre; TetO-KrasG12D; Rosa26(rtTa-IRES-EGFP) (iKras*) mice and LSL-KrasG12D mice bred with p48Cre mice (KC). Mice were given oral PD325901, a small-molecule inhibitor of MEK1 and MEK2 (factors in the MAPK signaling pathway), along with injections of cerulein to induce pancreatitis. Other mice were given PD325901 only after PanINs developed. Pancreatic tissues were collected and evaluated using histologic, immunohistochemical, immunofluorescence, and electron microscopy analyses. Acinar cells were isolated from the tissues and the effects of MEK1 and 2 inhibitors were assessed.Results PD325901 prevented PanIN formation, but not pancreatitis, in iKras* and KC mice. In iKras* or KC mice given PD325901 at 5 weeks after PanINs developed, PanINs regressed and acinar tissue regenerated. The regression occurred through differentiation of the PanIN cells to acini, accompanied by re-expression of the acinar transcription factor Mist1.Conclusions In iKras* and KC mice, MAPK signaling is required for the initiation and maintenance of pancreatic cancer precursor lesions. MAPK signaling promotes formation of PanINs by enabling dedifferentiation of acinar cells into duct-like cells that are susceptible to transformation.
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In an inducible system without tumor suppressor loss, PanINs can re-differentiate back to acinar cells after mutant Kras withdrawal.
“in such an inducible system, PanINs can be observed to re-differentiate back to acinar cells in the absence of tumor suppressor loss66.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [66]
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Epithelial-Myeloid cell crosstalk regulates acinar cell plasticity and pancreatic remodeling in mice
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“Conversely, inhibition of MAPK signaling using MEK inhibitors allows re-expression of acinar-specific transcription factors and re-differentiation of acinar cells (Collins et al., 2014).”
BackgroundMethodResultInfluentialSelf-citationEpithelial-Stromal Interactions in Pancreatic Cancer
Zhang, Y., Crawford, H. C., & di Magliano, M. P. (2018) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020518-114515 · Cited by 47 · see citing works
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Plasticity of differentiated cells in wound repair and tumorigenesis, part II: skin and intestine
Burclaff, J., & Mills, J. C. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.035071 · Cited by 45 · see citing works
“…et al., 2016b MAPK Required for SPEM Required for ADM Elevated in reprogrammed melanocytes Increased in dedifferentiation Khurana et al., 2013; Collins et al., 2014; Cammareri et al., 2017; Köhler et al., 2017 SOX9 Increased in SPEM cells Increased in ADM cells Increased in BCC…”
Subramani, R., Lopez-Valdez, R., Salcido, A., Boopalan, T., Arumugam, A., Nandy, S., & Lakshmanaswamy, R. (2014) · Experimental & Molecular Medicine · doi:10.1038/emm.2014.61 · Cited by 40 · see citing works
MECOM permits pancreatic acinar cell dedifferentiation avoiding cell death under stress conditions
Backx, E., Wauters, E., Baldan, J., Bulck, M. V., Michiels, E., Heremans, Y., Paep, D. L. D., Kurokawa, M., Goyama, S., Bouwens, L., et al. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-021-00771-6 · Cited by 37 · see citing works
“We confirmed this in 346 MECOM KO cells, where reduced activity of the ERK signaling pathway could be 347 directly linked to reduced acinar cell dedifferentiation, a process for which this signaling 348 pathway is critical (12, 44).”
BackgroundKhalafalla, F. G., & Khan, M. W. (2017) · Cancer Growth and Metastasis · doi:10.1177/1179064417709287 · Cited by 37 · see citing works
Mutant p53R270H drives altered metabolism and increased invasion in pancreatic ductal adenocarcinoma
Schofield, H. K., Zeller, J., Espinoza, C. E., Halbrook, C. J., Vecchio, A. D., Magnuson, B., Fabo, T., Daylan, A. E. C., Kovalenko, I., Lee, H., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.97422 · Cited by 38 · see citing works
“We, and others, have previously shown that MEK signaling regulates epithelial growth and differentiation as well as aspects of stroma activation and remodeling (23, 24, 26, 29).”
BackgroundResultSelf-citationPrevention and Reversion of Pancreatic Tumorigenesis through a Differentiation-Based Mechanism
Krah, N. M., Narayanan, S. M., Yugawa, D. E., Straley, J. A., Wright, C. V. E., MacDonald, R. J., & Murtaugh, L. C. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.07.012 · Cited by 37 · see citing works
Plasticity of differentiated cells in wound repair and tumorigenesis, part I: stomach and pancreas
Burclaff, J., & Mills, J. C. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.033373 · Cited by 36 · see citing works
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Therapeutic potential of targeting acinar cell reprogramming in pancreatic cancer
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Silencing Mist1 Gene Expression Is Essential for Recovery from Acute Pancreatitis
Karki, A., Humphrey, S. E., Steele, R. E., Hess, D. A., Taparowsky, E. J., & Konieczny, S. F. (2015) · PLoS ONE · doi:10.1371/journal.pone.0145724 · Cited by 32 · see citing works
TGIF1 functions as a tumor suppressor in pancreatic ductal adenocarcinoma
Parajuli, P., Singh, P., Wang, Z., Li, L., Eragamreddi, S., Ozkan, S., Ferrigno, O., Prunier, C., Razzaque, M. S., Xu, K., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018101067 · Cited by 30 · see citing works
“Interestingly, pharmacological inhibition of MEK/ERK signaling has been shown to suppress PDAC formation in KC mice, providing direct evidence that constitutive Kras/MEK/ERK plays a key role in PDAC pathogenesis (Collins et al , 2014).”
The EGFR-HSF1 axis accelerates the tumorigenesis of pancreatic cancer
Qian, W., Chen, K., Qin, T., Xiao, Y., Li, J., Yue, Y., Zhou, C., Ma, J., Duan, W., Lei, J., et al. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01823-4 · Cited by 30 · see citing works
“Considering that the abnormal activation of the normal EGFR pathway and its downstream MAPK/mTOR pathways followed by the KRAS oncogene mutation is essential to the initiation and progression of pancreatic cancer[53-55], these results remind us that EGFRHSF1 axis might participate in the pancreatic cancer initiation e…”
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“The MAPK pathway is not only involved in the formation and development of PC but also mediates the sensitivity of PC cells to chemotherapy drugs.(67,68) A similar function of ErbB signaling was reported in previous studies, and targeting the regulation of the ErbB pathway by sex-determining region Y-related high mobil…”
Quattrochi, B., Gulvady, A., Driscoll, D. R., Sano, M., Klimstra, D., Turner, C., & Lewis, B. (2017) · OncoTarget · doi:10.18632/oncotarget.16277 · Cited by 32 · see citing works
“In contrast, our studies demonstrate that ectopic mir-17~92 increases MEK/ERK signaling, a feature required for the maintenance of established PanIN lesions [6, 67], suggesting that elevated mir-17~92 levels should enhance pancreatic cancer development.”
Acinar cells and the development of pancreatic fibrosis
An, J., Jiang, T., Qi, L., & Xie, K. (2023) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2023.05.003 · Cited by 27 · see citing works
Ductal metaplasia in pancreas.
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“Another previous report revealed that MAPK signaling activation is required for the initiation and maintenance of pancreatic precancerous lesions in the PDAC mouse model (33).”
BackgroundLeal, A. S., Liu, P., Krieger-Burke, T., Ruggeri, B., & Liby, K. T. (2020) · Cancers · doi:10.3390/cancers13010096 · Cited by 23 · see citing works
Pharmacological inhibition and reversal of pancreatic acinar ductal metaplasia
Silva, L. D., Jiang, J., Perkins, C. M., Atanasova, K. R., Bray, J. K., Bulut, G. B., Azevedo‐Pouly, A. C. P., Campbell‐Thompson, M., Yang, X. T., Hakimjavadi, H., et al. (2022) · Cell Death Discovery · doi:10.1038/s41420-022-01165-4 · Cited by 23 · see citing works
“Cells were mixed with Matrigel and media and plated in 12-well chamber slides (Ibidi).”
MethodInfluentialMehra, S., Srinivasan, S., Singh, S. P., Zhou, Z., Garrido, V. T., Silva, I. D. C., Totiger, T. M., Dosch, A. R., Dai, X., Dawra, R. K., et al. (2022) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00159.2022 · Cited by 23 · see citing works
The Gut Microbiome and Pancreatic Cancer Development and Treatment
Attebury, H., & Daley, D. (2023) · The Cancer Journal · doi:10.1097/ppo.0000000000000647 · Cited by 23 · see citing works
Pancreatic acinar cell fate relies on system xC- to prevent ferroptosis during stress
Pan, Z., den Bossche, J.-L. V., Rodríguez-Aznar, E., Janssen, P., Lara, O., Ates, G., Massie, A., Paep, D. L. D., Houbracken, I., Mambretti, M., et al. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06063-w · Cited by 24 · see citing works
Jakubison, B. L., Schweickert, P. G., Moser, S. E., Yang, Y., Gao, H., Scully, K. M., Itkin‐Ansari, P., Liu, Y., & Konieczny, S. F. (2018) · Molecular Oncology · doi:10.1002/1878-0261.12314 · Cited by 23 · see citing works
“Indeed, work from the Pasca di Magliano Lab (Collins et al., 2012, 2014) has shown that precancerous PDAC lesions exhibit plasticity and can be reverted back to healthy pancreatic acinar tissue upon loss of oncogenic KRAS signaling.”
BackgroundMeyers, N., Gérard, C., Lemaigre, F. P., & Jacquemin, P. (2020) · Scientific Reports · doi:10.1038/s41598-020-62106-8 · Cited by 21 · see citing works
The Integrated Stress Response in Pancreatic Development, Tissue Homeostasis, and Cancer
Malnassy, G., Ziolkowski, L. M., Macleod, K. F., & Oakes, S. A. (2024) · Gastroenterology · doi:10.1053/j.gastro.2024.05.009 · Cited by 21 · see citing works
Beta 1 integrin signaling mediates pancreatic ductal adenocarcinoma resistance to MEK inhibition
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ELAPOR1 is a secretory granule maturation-promoting factor that is lost during paligenosis
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Method for improved integrity of RNA isolated from Matrigel cultures
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Transcriptional Profile of Human Pancreatic Acinar Ductal Metaplasia
Jiang, J., Hakimjavadi, H., Bray, J. K., Perkins, C. M., Gosling, A., daSilva, L., Bulut, G. B., Ali, J., Setiawan, V. W., Campbell‐Thompson, M., et al. (2023) · Gastro Hep Advances · doi:10.1016/j.gastha.2023.02.003 · Cited by 17 · see citing works
The secret origins and surprising fates of pancreas tumors
Bailey, J. M., DelGiorno, K. E., & Crawford, H. C. (2014) · Carcinogenesis · doi:10.1093/carcin/bgu056 · Cited by 17 · see citing works
“(64), who showed that inhibition of MEK, a downstream target of Kras*, leads to regression of early mPanIN by forcing redifferentiation of the neoplasia to acinar cells.”
BackgroundHuang, X., Bhugul, P. A., Fan, G., Ye, T., Huang, S., Dai, S., Chen, B., & Zhou, M. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.8327 · Cited by 17 · see citing works
“Also, the downward pathways of EGFR, such as mitogen-activated protein kinase signaling and phosphatidyl inositol 3-kinase signaling, are required for PanIN formation and pancreatic carcinogenesis (13,14).”
Targeting ribosome biogenesis reinforces ERK-dependent senescence in pancreatic cancer
Rowell, M., Deschênes‐Simard, X., Lopes‐Paciencia, S., Calvé, B. L., Kalegari, P., Mignacca, L., Ruiz, A. F., Guillon, J., Lessard, F., Bourdeau, V., et al. (2023) · Cell Cycle · doi:10.1080/15384101.2023.2278945 · Cited by 16 · see citing works
“This is consistent with a proposed role for ERK activation in the ded-ifferentiation of acinar cells during ADM [16].”
BackgroundLoss of RE-1 silencing transcription factor accelerates exocrine damage from pancreatic injury
Bray, J. K., Elgamal, O. A., Jiang, J., Wright, L. S., Sutaria, D. S., Badawi, M. A., Borcyk, M. G., Liu, X., Fredenburg, K. M., Campbell‐Thompson, M., et al. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-2269-7 · Cited by 16 · see citing works
Bangs, F. K., Miller, P. F., & O’Neill, E. E. (2020) · Disease Models & Mechanisms · doi:10.1242/dmm.044289 · Cited by 16 · see citing works
Deletion of Histone Methyltransferase G9a Suppresses Mutant Kras-driven Pancreatic Carcinogenesis
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Döppler, H. R., Liou, G., & Störz, P. (2022) · Antioxidants · doi:10.3390/antiox11010137 · Cited by 16 · see citing works
The Role of Krüppel-like Factors in Pancreatic Physiology and Pathophysiology
Giarrizzo, M., LaComb, J. F., & Bialkowska, A. B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108589 · Cited by 14 · see citing works
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Novel strategy for oncogenic alteration-induced lipid metabolism reprogramming in pancreatic cancer
Guo, D., Ye, L., Wu, W., Yu, X., & Jin, K. (2023) · Acta Biochimica et Biophysica Sinica · doi:10.3724/abbs.2023045 · Cited by 13 · see citing works
“Furthermore, the MAPK signaling pathway was proven to be required for the formation of PanINs in mice because it promotes the dedifferentiation of acinar cells into duct-like cells, which are easily transformed [37].”
Fey, S. K., Najumudeen, A. K., Watt, D. M., Millett, L. M., Ford, C. A., Gilroy, K. L., Simpson, R. J., McLay, K., Upstill‐Goddard, R., Chang, D. K.-F., et al. (2024) · Cancer Research · doi:10.1158/0008-5472.can-23-2709 · Cited by 11 · see citing works
“Given the increased PanIN burden and MAPK signaling in the pancreata of KC Kras G12D/fl mice, we determined whether these PanIN lesions were sensitive to therapeutic targeting of the MAPK pathway, as has previously been reported in KC Kras G12D/+ mice (29, 30).”
Murine Models of Pancreatitis Leading to the Development of Pancreatic Cancer
Leal, A. S., & Liby, K. T. (2018) · Current Protocols in Pharmacology · doi:10.1002/cpph.48 · Cited by 11 · see citing works
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“RAS-stimulated signaling of MAPK has been reported to be tightly activated in pancreatic cancer, responsible for the initiation and maintenance of pancreatic carcinogenesis [48].”
BackgroundETV5 regulates ductal morphogenesis with Sox9 and is critical for regeneration from pancreatitis
Das, K. K., Heeg, S., Pitarresi, J. R., Reichert, M., Bakir, B. S., Takano, S., Kopp, J. L., Wahl‐Feuerstein, A., Hicks, P. D., Sander, M., et al. (2018) · Developmental Dynamics · doi:10.1002/dvdy.24626 · Cited by 10 · see citing works
“In addition to a ductal morphology, ADM cells co-express acinar and ductal markers and exhibit up-regulation of signaling pathways such as epidermal growth factor receptor (EGFR) and NOTCH, and downstream effectors such as the KRASMEK-MAPK pathway, which are increased during pancreatic tumorigenesis (Miyamoto et al.,…”
Cellular collusion: cracking the code of immunosuppression and chemo resistance in PDAC
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Srinivasan, S., Mehra, S., Jinka, S., Bianchi, A., Singh, S. P., Dosch, A. R., Amirian, H., Krishnamoorthy, V., Silva, I. D. C., Patel, M. S., et al. (2025) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2025.101606 · Cited by 9 · see citing works
“10,11 12–14 Building on our lab’s long standing efforts in understanding the multifaceted role of transcription factor signaling in pancreatitis and pancreatic cancer, we have previously identified hyperactivation of cyclic adenosine monophosphate response element-binding protein 1 (CREB) via…”
Clinical significance of pancreatic ductal metaplasia
Jiang, T., Fang, W., & Xie, K. (2022) · The Journal of Pathology · doi:10.1002/path.5883 · Cited by 8 · see citing works
“Likewise, PDM could be formed by the reversal of PanIN, given the plasticity of PanIN [101].”
BackgroundInfluentialJing, T., Xu, X., Wu, C., Wei, D., Yuan, L., Huang, Y., Liu, Y., & Wang, B. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216444 · Cited by 8 · see citing works
Murugesan, P., Begum, H., & Tangutur, A. D. (2022) · Gene · doi:10.1016/j.gene.2022.147092 · Cited by 8 · see citing works
Kiemen, A. L., Almagro-Pérez, C., Matos, V., Forjaz, A., Braxton, A. M., Dequiedt, L., Parksong, J., Cannon, C. D., Yuan, X., Shin, S. M., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.08.03.606493 · Cited by 8 · see citing works
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Li, X., He, J., & Xie, K. (2022) · Cellular Oncology · doi:10.1007/s13402-022-00664-x · Cited by 6 · see citing works
“Alternatively, PDM may be formed by the reversal of PanIN, given the plasticity of PanIN [77].”
BackgroundInfluentialWaldron, R. T. (2015) · doi:10.3998/panc.2015.41 · Cited by 6 · see citing works
Inflammation and de-differentiation in pancreatic carcinogenesis
Seimiya, T., Otsuka, M., Iwata, T., Tanaka, E., Suzuki, T., Sekiba, K., Yamagami, M., Ishibashi, R., & Koike, K. (2018) · World Journal of Clinical Cases · doi:10.12998/wjcc.v6.i15.882 · Cited by 5 · see citing works
Metabolism Drives Carcinogenesis and Maintenance of Pancreatic Tumors
Halbrook, C. J., Nelson, B. S., & Lyssiotis, C. A. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0034 · Cited by 5 · see citing works
Exome Sequencing of Pancreatic Acinar Carcinoma Identified Distinctive Mutation Patterns
Liu, Y., Raimondo, M., Wallace, M. B., Mody, K., Stauffer, J. A., Zhang, L., Ji, B., & Bi, Y. (2021) · Pancreas · doi:10.1097/mpa.0000000000001870 · Cited by 5 · see citing works
“In ACC, the MAPK pathway is also critical for acinar cell physiologic function and maintains its differentiation.(54) Comprehensive genomic analysis showed that approximately 23% of ACC tumors had recurrent rearrangement involving BRAF and RAF1, resulting in MAPK pathway activation, which can be abrogated by theMAPK k…”
BackgroundOncogenic KRAS, Mucin 4, and Activin A‐Mediated Fibroblast Activation Cooperate for PanIN Initiation
Hu, C., Huang, C., Hsu, M., Chien, H., Wu, P., Chen, Y., Jeng, Y., Tang, S., Chung, M., Shen, C., et al. (2023) · Advanced Science · doi:10.1002/advs.202301240 · Cited by 5 · see citing works
Stabilization of HIF-2α impacts pancreas growth
Flores-Martinez, Á., García-Núñez, A., Rojas, A., & Cano, D. (2018) · Scientific Reports · doi:10.1038/s41598-018-32054-5 · Cited by 3 · see citing works
MAPK Signaling and the Tumor Microenvironment: Drivers of Cancer Development and Resistance
Owida, H. A., Mohammad, S. I., Patel, P. N., Roopashree, R., Vasudevan, A., Arora, V., Nayak, P. P., Shukla, S. K., Hjazi, A. M., & Hsu, C.-Y. (2026) · DNA and Cell Biology · doi:10.1177/10445498261417426 · Cited by 4 · see citing works
“Inhibition of MAPK signaling has been shown to partially rescue aspects of dedifferentiation by rep-rioritizing acinar cell differentiation back (Collins et al., 2014).”
Yang, H.-J., Song, B., Sim, B., Jung, Y., Chae, U., Lee, D. G., Cha, J., Baek, S.-J., Lim, K. S., Choi, W. S., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228820 · Cited by 4 · see citing works
“Therefore, the importance of the MAPK signaling pathway is supported by its promotion of PanIN, which renders ADM susceptible to transformation [40].”
BackgroundSavary, C., Picard, C., Corradini, N., & Castets, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116310 · Cited by 5 · see citing works
Juin, A., Spence, H. J., & Machesky, L. M. (2024) · The Journal of Pathology · doi:10.1002/path.6248 · Cited by 4 · see citing works
“To identify the mechanisms by which MAP4K4 drives PDAC tumorigenesis, we investigated the functional interplay between MAP4K4 and signalling pathways frequently activated during pancreatic intraepithelial neoplasia development [10,37,39].”
BackgroundOncogenic KRAS/ERK/JUNB signaling suppresses differentiation regulator GATA6 in pancreatic cancer
Zhong, Z., Cao, X., Liao, P.-J., Sethi, R., Klomp, J. A., Stalnecker, C. A., Chen, J., Wan, Y., Der, C. J., & Virshup, D. M. (2025) · Journal of Clinical Investigation · doi:10.1172/jci191370 · Cited by 3 · see citing works
Wei, F., Zou, Q., An, J., Zhang, T., Sun, Q., Li, X., Jiang, T., Zhu, X., Wen, T., He, J., et al. (2026) · Gastroenterology · doi:10.1053/j.gastro.2026.02.033 · Cited by 3 · see citing works
- Authors
- Collins, M. A., Yan, W., Sebolt–Leopold, J. S., & Pasca di Magliano, M.
- Affiliations
- University of Michigan (US)
- ORCID
- Yan, Wei
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 146
- Issue
- 3
- Pages
- 822-834.e7
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC4037403
- OpenAlex
- W2010171965
- Cited by
- 133
- References
- 46
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 8 · 2023: 19 · 2022: 12 · 2021: 11 · 2020: 15 · 2019: 6 · 2018: 14 · 2017: 11 · 2016: 8 · 2015: 11 · 2014: 3
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA151588, P50CA130810, R01CA155198, P50CA13810)
- National Institute of General Medical Sciences (T32GM07315, T32GM007315)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (5-T32-HD007515, T32HD007505)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- MAPK signaling, pancreatic intraepithelial neoplasia, KRAS G12D, pancreatic carcinogenesis, MEK1/2 inhibition, pancreatitis, Mist1, pancreatic cancer precursor lesions
- MeSH terms
- Animals, Carcinoma in Situ, Disease Models, Animal, Female, Male, Mice, Mutant Strains, Pancreatic Neoplasms, Pancreatitis, Signal Transduction, Up-Regulation, Mitogen-Activated Protein Kinase Kinases, MAP Kinase Signaling System, MAP Kinase Kinase 1, MAP Kinase Kinase 2, Mice, Cell Dedifferentiation, Acinar Cells
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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