pdx1 cre mice  (Jackson Laboratory)

Journal: Oncogene

Article Title: Role of SCAP in regulation of pancreatic homeostasis, pancreatitis, and tumorigenesis

doi: 10.1038/s41388-026-03784-y

Figure Lengend Snippet: A GSEA analysis of upregulated and downregulated Hallmark genesets in the Scap Δpanc compared to Scap f/f acinar cluster. B IPA upstream regulator analysis of predicted upregulated and downregulated signaling pathways in the Scap Δpanc acinar cluster compared to Scap f/f . C Enrichr analysis of Jensen DISEASES genesets associated with genes overexpressed in Scap Δpanc versus Scap f/f acinar cells. D GSEA analysis of upregulated and downregulated Hallmark genesets in the Scap Δpanc compared to Scap f/f exocrine cluster. E IPA analysis of predicted upregulated and downregulated signaling pathways associated with observed gene expression changes in the Scap Δpanc versus Scap f/f exocrine cluster. F A UMAP projection of Scap Δpanc (left) and Scap f/f (right) pancreatic exocrine and acinar cells. Point color—from blue (early pseudotime, least differentiated, expressing genes Pdx1 , Hnf1b , Sox9 , Ptf1a ) through yellow (intermediate) to red (late pseudotime, most differentiated, expressing genes Amy2a , Cpa1 , Prss1 , Krt19 )—reflects Monocle 3-inferred differentiation progression, showing that Scap Δpanc cells are restricted to the middle differentiation stages while Scap f/f cells had both earlier and later differentiation states. G A violin plot showing the quantification of the pseudotime distribution of Scap Δpanc and Scap f/f clusters. H A UMAP projection of pseudotime values split into three equally populated bins (Early, Middle, and Late) using quantile-based tertile cuts. I Bar chart of percentage of cells in Scap Δpanc and Scap f/f samples by pseudotime stage. J Graphical abstract describing how the loss of Scap impacts the pancreas. Created in BioRender. Lilly, A. (2026) https://BioRender.com/511uib5 . *** p ≤ 0.001, in all panels. Chi-square test used for quantification of percentage of cells by pseudotime stage.

Article Snippet: The analysis used Pdx1-Cre mice ([ ], Jax#014647, RRID:IMSR_JAX:014647) and Scap f/f mice ([ ], Jax#004162, RRID:IMSR_JAX:004162) obtained from Jackson laboratory (Bar Harbor, ME).

Techniques: Protein-Protein interactions, Gene Expression, Expressing

Journal: Cancer Research Communications

Article Title: The Lysine Demethylase KDM4C Is an Oncogenic Driver and Regulates ERK Activity in KRAS-Mutant Pancreatic Ductal Adenocarcinoma

doi: 10.1158/2767-9764.CRC-25-0278

Figure Lengend Snippet: CRISPR-mediated KDM4C deletion attenuates PDAC growth in vitro and in vivo . A, Western blot showing KDM4C depletion in selected AsPC1 and KPC-mT4 KDM4C -null clones. B, Colony formation assay (CFA): representative wells comparing AsPC1 cells to KDM4C KO isogenic cells show reduced colony formation ability in the absence of KDM4C. C, Quantification of CFA by ImageJ shows a significant reduction in the number of colonies in KDM4C KO cells compared with KDM4C WT cells; P value was determined by one-way ANOVA test; *, P ≤ 0.05; **, P ≤ 0.01. D, Proliferation assay measured through % confluence over time by the Incucyte Live Imaging system shows decreased proliferation in the absence of KDM4C, P value determined by one-way ANOVA test. E, Kaplan–Meier survival plot showing increased survival of B6 mice orthotopically transplanted with KDM4C KO KPC-mT4 cells compared with those transplanted with KDM4C WT KPC-mT4 ( n = 6 per arm).

Article Snippet: Human PDAC cell lines AsPC1 (RRID: CVCL_0152) and Pa03C (RRID: CVCL_E301) and murine PDAC cell line derived from KRAS LSL-G12D/+ , Trp53 LSL-R172H/+ , Pdx1-Cre (KPC) mice KPC mT4 (Dr. David Tuveson, Cold Spring Harbor Laboratories; ref. ) as well as HPNE (RRID: CVCL_C466) and HEK293 cell lines (RRID: CVCL_0045) were used.

Techniques: CRISPR, In Vitro, In Vivo, Western Blot, Clone Assay, Colony Assay, Proliferation Assay, Imaging

Journal: Cancer Research Communications

Article Title: The Lysine Demethylase KDM4C Is an Oncogenic Driver and Regulates ERK Activity in KRAS-Mutant Pancreatic Ductal Adenocarcinoma

doi: 10.1158/2767-9764.CRC-25-0278

Figure Lengend Snippet: KDM4C expression correlates with ERK activity. A, Top enriched IPA pathways from RNA-seq data from KDM4C KO vs. WT AsPC1 are cell-cycle arrest, inhibition of MEK/ERK, protein synthesis inhibition, and increased oxidative phosphorylation and apoptosis, whereas ATF4, MYC, and ERK1/2 are among the top downregulated networks. B, GSEA plot from RNA-seq data showing downregulated KRAS and MYC signatures in KDM4C -depleted cells. C, RPPA data demonstrate downregulation of the ERK pathway in two different KDM4C -null clones. D, Western blot validating downregulation of ERK phosphorylation in human PDAC cell line AsPC1 and in mouse PDAC cell line (KPC-mT4) KDM4C KO clones. E, Representative micrographs of pERK expression by IHC in PDAC tumors harvested at day 30 from mice injected with PDAC cell line KPC-mT4 demonstrates downregulation of pERK in the KDM4C KO clones compared with untreated KPC-mT4 (Scale bar, 100 μm).

Article Snippet: Human PDAC cell lines AsPC1 (RRID: CVCL_0152) and Pa03C (RRID: CVCL_E301) and murine PDAC cell line derived from KRAS LSL-G12D/+ , Trp53 LSL-R172H/+ , Pdx1-Cre (KPC) mice KPC mT4 (Dr. David Tuveson, Cold Spring Harbor Laboratories; ref. ) as well as HPNE (RRID: CVCL_C466) and HEK293 cell lines (RRID: CVCL_0045) were used.

Techniques: Expressing, Activity Assay, RNA Sequencing, Inhibition, Phospho-proteomics, Clone Assay, Western Blot, Injection

Journal: Cancer Research Communications

Article Title: The Lysine Demethylase KDM4C Is an Oncogenic Driver and Regulates ERK Activity in KRAS-Mutant Pancreatic Ductal Adenocarcinoma

doi: 10.1158/2767-9764.CRC-25-0278

Figure Lengend Snippet: Compensatory upregulation of KDM4A restores cell-intrinsic ERK signaling in KDM4C -null cells but not immune surveillance. A, Western blot panel shows that late-passage KDM4C KO clones of both AsPC1 and KPC-mT4 (KO-late) restored pERK levels. B–D, ERK reactivation rescues the reduction in colony formation and proliferation in both AsPC1 and KPC-mT4 KO cells observed in earlier passages. Bar plots show number of colonies calculated by ImageJ. For each sample, two wells have been analyzed, and the statistical significance is calculated using one-way ANOVA. For both AsPC1 and KPC-mT4 cells, the difference between parental and adapted KDM4C KO clones was not significant. E, Lentiviral shRNA knockdown of KDM4C recapitulates the adaptation to KDM4C depletion in adapted cells. Western blot panel compares early-passage (day 7 after transduction) and late-passage (day 40 after transduction) in AsPC1 cells. Late-passage KDM4C knockdown cells have adapted to the loss of KDM4C and restored ERK activation. F, Western blot validating KDM4A upregulation in adapted KPC-mT4 KDM4C KO clones. G, RNA-seq results from AsPC1 early-passage KDM4C KO cells correlate with the ERK inhibitor (ERKi) transcriptome signature, whereas late-passage adapted cells are inversely correlated. H and I, Bar graphs showing significant reduction in the tumor growth of adapted KPC-mT4 KDM4C KO cells when transplanted into the immunocompetent B6 mice compared with KDM4C WT control ( n = 5), whereas the reverse is observed when the same cells are transplanted into immune-compromised athymic mice ( n = 8), significance determined by unpaired t test; *, P ≤ 0.05.

Article Snippet: Human PDAC cell lines AsPC1 (RRID: CVCL_0152) and Pa03C (RRID: CVCL_E301) and murine PDAC cell line derived from KRAS LSL-G12D/+ , Trp53 LSL-R172H/+ , Pdx1-Cre (KPC) mice KPC mT4 (Dr. David Tuveson, Cold Spring Harbor Laboratories; ref. ) as well as HPNE (RRID: CVCL_C466) and HEK293 cell lines (RRID: CVCL_0045) were used.

Techniques: Western Blot, Clone Assay, shRNA, Knockdown, Transduction, Activation Assay, RNA Sequencing, Control

Journal: Cancer Research Communications

Article Title: The Lysine Demethylase KDM4C Is an Oncogenic Driver and Regulates ERK Activity in KRAS-Mutant Pancreatic Ductal Adenocarcinoma

doi: 10.1158/2767-9764.CRC-25-0278

Figure Lengend Snippet: Pan-KDM4 Inhibitor TACH107 reduces proliferation and colony formation in PDAC cell lines in vitro and increases survival in vivo . A, MTT assay shows reduced proliferation in PDAC cell lines following TACH107 treatment, significance determined by one-way ANOVA. B, Reduced colony formation ability of human and mouse PDAC cell lines upon treatment with varying doses of TACH107 and ( C ) Quantification of the number of colonies, one-way ANOVA was used to assess significance. D, Survival plot showing B6 mice transplanted with PDAC cell line KPC-mT4 and treated with TACH107 survive longer than those treated with vehicle only ( n = 3). E, Results from CETSA show increased heat stability of KDM4 proteins when treated with TACH107 vs. DMSO. F, Representative IF images showing increased H3K9me3 signal after TACH107 treatment compared with control cells. G, Normalized fluorescence intensity of H3K9me3 signal calculated by the corrected total cell fluorescence method using ImageJ, significance determined via unpaired Student t test. For all plots; * is P ≤ 0.05; ** is P ≤ 0.01; *** is P ≤ 0.001; and **** is P ≤ 0.0001. H, Representative micrographs showing H3K9me3 levels by IHC in PDAC tumors harvested on day 30 from mice injected with PDAC cell line KPC-mT4 demonstrate increased H3K9me3 mark in the TACH107 treated mice compared with vehicle control mice. Scale bar, 100 μm. I, Quantification of the area of positive staining in H using ImageJ color deconvolution plugin for IHC DAB staining, the difference between vehicle-treated and TACH107-treated samples is statistically significant.

Article Snippet: Human PDAC cell lines AsPC1 (RRID: CVCL_0152) and Pa03C (RRID: CVCL_E301) and murine PDAC cell line derived from KRAS LSL-G12D/+ , Trp53 LSL-R172H/+ , Pdx1-Cre (KPC) mice KPC mT4 (Dr. David Tuveson, Cold Spring Harbor Laboratories; ref. ) as well as HPNE (RRID: CVCL_C466) and HEK293 cell lines (RRID: CVCL_0045) were used.

Techniques: In Vitro, In Vivo, MTT Assay, Control, Fluorescence, Injection, Staining