FB2026_03 , released September 17, 2026
Human Disease Model Report: pancreatic carcinoma, multigenic
Open Close
General Information
Name
pancreatic carcinoma, multigenic
FlyBase ID
FBhh0001548
Disease Ontology Term
Parent Disease
Overview

This report describes a multigenic model of pancreatic carcinoma (pancreatic ductal adenocarcinoma) using a combination of Drosophila genes related to a number of human genes implicated in this disease: human KRAS (using an activated form of Dmel\Ras85D), human TP53 (using RNAi-knockdown targeted to Dmel\p53), and human SMAD4 (using RNAi-knockdown targeted to Dmel\Med). Action of a fourth human gene, CDKN2A, was approximated by targeted expression of Dmel\CycE (both are involved in regulation of the mitotic cell cycle).

UAS constructs of human genes Hsap\KRAS, Hsap\TP53, and Hsap\SMAD4 have been introduced into flies, but have not been used in the context of this disease model.

'4-hit' flies were generated using various GAL4 drivers. Wing-specify drivers resulted in epithelial transformations in the wing consistent with uncontrolled growth. More general GAL4 drivers resulted in decreased survival. A genetic screen identified MEK and AURKB as potential therapeutic targets.

[updated Dec. 2023 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: pancreatic carcinoma, multigenic
OMIM report

[PANCREATIC CANCER](https://omim.org/entry/260350)

Human gene(s) implicated

[KRAS PROTOONCOGENE, GTPase; KRAS](https://omim.org/entry/190070)

[ACTIVIN A RECEPTOR, TYPE IB; ACVR1B](https://omim.org/entry/601300)

[TUMOR PROTEIN p53; TP53](https://omim.org/entry/191170)

[SMAD FAMILY MEMBER 4; SMAD4](https://omim.org/entry/600993)

[SERINE/THREONINE PROTEIN KINASE 11; STK11](https://omim.org/entry/602216)

Symptoms and phenotype

Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent neoplastic disease of the pancreas accounting for more than 90% of all pancreatic malignancies. PDAC is the fourth most frequent cause of cancer-related deaths worldwide with a 5-year overall survival of less than 8%. (Orth et al., 2019; pubmed:31395068)

Pancreatic cancer shows among the highest mortality rates of any cancer, with a 5-year relative survival rate of less than 5%. By the time of initial diagnosis, metastatic disease is commonly present. [from MIM:260350; 2023.12.12]

Genetics

Somatic mutations in pancreatic cancer occur in the KRAS, CDKN2A, SMAD4, TP53, ARMET, STK11, ACVR1B, and RBBP8 genes. [from MIM:260350; 2023.12.12]

Cellular phenotype and pathology
Molecular information
External links
Disease synonyms
pancreatic cancer, somatic
pancreatic ductal adenocarcinoma
PDAC
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

One to one: 1 human gene to 1 Drosophila gene; multiple related genes in both species.

Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to one: 3 human genes to 1 Drosophila gene; multiple related genes in both species.

Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to one: 3 human genes to 1 Drosophila gene.

Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

No moderate- to high-scoring ortholog of CDKN2A has been identified in Drosophila.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (4)
    Gene Snapshot
    Ras oncogene at 85D (Ras85D) encodes a protein that acts downstream of several cell signals, most notably from Receptor Tyrosine Kinases, to regulate tissue growth and development. When abnormally activated it can direct developmental defects and tissue hyperplasia, mimicking aspects of human disease including Rasopathies and cancer, respectively. [Date last reviewed: 2019-03-14]
    Cellular component (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    High-scoring ortholog of human KRAS, HRAS, and NRAS (1 Drosophila to 3 human; multiple related genes in both species).

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Gene Snapshot
    p53 (p53) encodes a transcriptional factor required for adaptive responses to genotoxic stress, including cell death, compensatory proliferation and DNA repair. [Date last reviewed: 2019-03-14]
    Cellular component (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    Moderate-scoring ortholog of human TP53, TP63, TP73 (1 Drosophila to 3 human).

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Gene Groups / Pathways
    Comments on ortholog(s)
    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Gene Snapshot
    Medea (Med) encodes a protein that belongs to the highly conserved Smad family. It can bind its siblings encoded by Mad or Smox to facilitate signal transduction for the product of dpp or Activin ligands in the TGF-beta family. Med-complexes function as transcriptional regulators. Many developmental roles include dorsal-ventral patterning, patterning and proliferation of the wing disc and gene expression in the mushroom body of the larval brain. [Date last reviewed: 2019-03-14]
    Gene Groups / Pathways
    Comments on ortholog(s)

    High-scoring ortholog of human SMAD4 (1 Drosophila to 1 human; multiple related genes in both species).

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (185 groups)
      protein-protein
      Interacting group
      Assay
      References
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      pull down, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      two hybrid, anti tag coimmunoprecipitation, autoradiography
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      gtpase assay, autoradiography
      anti tag coimmunoprecipitation, peptide massfingerprinting
      two hybrid, pull down, western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      two hybrid, anti tag coimmunoprecipitation, anti tag western blot, pull down
      pull down, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, Identification by mass spectrometry, pull down, covalent binding, western blot
      protein-protein
      Interacting group
      Assay
      References
      anti tag coimmunoprecipitation, western blot, pull down, autoradiography, coimmunoprecipitation, anti tag western blot
      bimolecular fluorescence complementation, fluorescence microscopy
      pull down, autoradiography
      pull down, western blot, anti tag coimmunoprecipitation, anti tag western blot
      pull down, autoradiography
      pull down, autoradiography
      anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      anti tag coimmunoprecipitation, western blot
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based, two hybrid array
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, western blot, autoradiography, anti tag coimmunoprecipitation, anti tag western blot
      pull down, autoradiography
      pull down, autoradiography
      two hybrid, anti tag coimmunoprecipitation, western blot
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      two hybrid, pull down, autoradiography
      anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, western blot, anti bait coimmunoprecipitation
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      anti bait coimmunoprecipitation, western blot
      pull down, autoradiography
      pull down, autoradiography
      anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
      anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based, anti bait coimmunoprecipitation, western blot
      anti bait coimmunoprecipitation, western blot
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      two hybrid, pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      anti tag coimmunoprecipitation, anti tag western blot, western blot, anti bait coimmunoprecipitation, pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      bimolecular fluorescence complementation, fluorescence microscopy, two hybrid array
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      enzymatic study, western blot
      anti tag coimmunoprecipitation, western blot
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      two hybrid, pull down, autoradiography
      pull down, autoradiography
      two hybrid, pull down, autoradiography
      anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
      pull down, autoradiography
      anti bait coimmunoprecipitation, western blot
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      two hybrid array, pull down, autoradiography
      pull down, autoradiography
      pull down, autoradiography
      two hybrid, pull down, autoradiography
      anti tag coimmunoprecipitation, western blot, pull down, anti tag western blot, coimmunoprecipitation
      bimolecular fluorescence complementation, fluorescence microscopy
      pull down, autoradiography
      enzymatic study, western blot
      anti bait coimmunoprecipitation, western blot
      pull down, autoradiography
      anti tag coimmunoprecipitation, anti tag western blot
      RNA-RNA
      Interacting group
      Assay
      References
      luminiscence technology, fluorescence technology
      luminiscence technology
      luminiscence technology, fluorescence technology
      luminiscence technology, fluorescence technology, necessary binding region
      luminiscence technology
      protein-protein
      Interacting group
      Assay
      References
      anti tag coimmunoprecipitation, anti tag western blot, pull down, western blot
      anti tag coimmunoprecipitation, anti tag western blot
      anti bait coimmunoprecipitation, western blot, experimental knowledge based, anti tag coimmunoprecipitation, anti tag western blot
      anti bait coimmunoprecipitation, anti tag western blot
      anti bait coimmunoprecipitation, western blot
      pull down, western blot
      anti bait coimmunoprecipitation, western blot
      anti tag coimmunoprecipitation, western blot
      anti bait coimmunoprecipitation, western blot, pull down
      two hybrid, surface plasmon resonance, anti bait coimmunoprecipitation, peptide massfingerprinting, pull down, autoradiography
      protein-protein
      Interacting group
      Assay
      References
      anti tag coimmunoprecipitation, anti tag western blot
      two hybrid, anti tag coimmunoprecipitation, anti tag western blot
      pull down, autoradiography, two hybrid
      anti tag coimmunoprecipitation, autoradiography, pull down, tag visualisation, anti tag western blot
      fluorescent resonance energy transfer, fluorescence microscopy, anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, anti tag western blot
      RNA-RNA
      Interacting group
      Assay
      References
      luminiscence technology
      Alleles Reported to Model Human Disease (Disease Ontology) (72 alleles)
      Models Based on Experimental Evidence ( 2 )
      Modifiers Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Interaction
      References
      Models Based on Experimental Evidence ( 5 )
      Modifiers Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Interaction
      References
      Models Based on Experimental Evidence ( 17 )
      Allele
      Disease
      Evidence
      References
      model of  cancer
      Modifiers Based on Experimental Evidence ( 19 )
      Allele
      Disease
      Interaction
      References
      model of  cancer
      is exacerbated by ITPUAS.F
      model of  cancer
      is ameliorated by InRGL00139
      is ameliorated by InRJF01183
      is ameliorated by InRJF01482
      is ameliorated by NetBΔ
      is ameliorated by NetBKK103672
      is ameliorated by unc-5MI04273
      is ameliorated by JraNIG.2275R
      is ameliorated by bskDN.UAS
      is ameliorated by bskHMS00777
      is exacerbated by hepAct.UAS
      is exacerbated by imdUAS.cGa
      is ameliorated by TimpUAS.cPa
      ameliorates  cancer
      model of  kidney cancer
      is ameliorated by Pka-C1B3
      is ameliorated by mTorΔP
      model of  cancer
      is exacerbated by Ptp61FΔ
      is exacerbated by exe1
      is exacerbated by M6W186stop
      is ameliorated by Ptip3804
      is exacerbated by p53UAS.cUa
      is ameliorated by Ilp8MI00727
      is exacerbated by Clbn1Q
      exacerbates  carcinoma
      model of  carcinoma
      is exacerbated by NkapGD11807
      Models Based on Experimental Evidence ( 11 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 15 )
      Allele
      Disease
      Interaction
      References
      Models Based on Experimental Evidence ( 3 )
      Modifiers Based on Experimental Evidence ( 5 )
      Models Based on Experimental Evidence ( 6 )
      Modifiers Based on Experimental Evidence ( 5 )
      Alleles Representing Disease-Implicated Variants
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Related mammalian, viral, bacterial, or synthetic transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      loss of function allele
      loss of function allele
      P-element activity
      amorphic allele - genetic evidence
      amorphic allele - genetic evidence
      ends-in gene targeting
      amorphic allele - molecular evidence
      Delta2-3 transposase
      amorphic allele - molecular evidence
      Delta2-3 transposase
      ends-in gene targeting
      loss of function allele
      ethyl methanesulfonate
      ethyl methanesulfonate
      ethyl methanesulfonate
      loss of function allele
      loss of function allele
      ethyl methanesulfonate
      loss of function allele
      References (7)