title: Mucin (Muc) expression during pancreatic cancer progression in spontaneous mouse model: potential implications for diagnosis and therapy.
abstract: BACKGROUND
  Pancreatic cancer (PC) is a lethal malignancy primarily driven by activated Kras mutations and characterized by the deregulation of several genes including mucins. Previous studies on mucins have identified their significant role in both benign and malignant human diseases including PC progression and metastasis. However, the initiation of MUC expression during PC remains unknown because of lack of early stage tumor tissues from PC patients.
  
  
  METHODS
  In the present study, we have evaluated stage specific expression patterns of mucins during mouse PC progression in (Kras(G12D);Pdx1-Cre (KC)) murine PC model from pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC) by immunohistochemistry and quantitative real-time PCR.
  
  
  RESULTS
  In agreement with previous studies on human PC, we observed a progressive increase in the expression of mucins particularly Muc1, Muc4 and Muc5AC in the pancreas of KC (as early as PanIN I) mice with advancement of PanIN lesions and PDAC both at mRNA and protein levels. Additionally, mucin expression correlated with the increased expression of inflammatory cytokines IFN-γ (p < 0.0062), CXCL1 (p < 0.00014) and CXCL2 (p < 0.08) in the pancreas of KC mice, which are known to induce mucin expression. Further, we also observed progressive increase in inflammation in pancreas of KC mice from 10 to 50 weeks of age as indicated by the increase in the macrophage infiltration. Overall, this study corroborates with previous human studies that indicated the aberrant overexpression of MUC1, MUC4 and MUC5AC mucins during the progression of PC.
  
  
  CONCLUSIONS
  Our study reinforces the potential utility of the KC murine model for determining the functional role of mucins in PC pathogenesis by crossing KC mice with corresponding mucin knockout mice and evaluating mucin based diagnostic and therapeutic approaches for lethal PC.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA.
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Rachagani
authors.forename: María P
authors.initials: MP
authors.lastname: Torres
authors.forename: Sushil
authors.initials: S
authors.lastname: Kumar
authors.forename: Dhanya
authors.initials: D
authors.lastname: Haridas
authors.forename: Michael
authors.initials: M
authors.lastname: Baine
authors.forename: Muzafar A
authors.initials: MA
authors.lastname: Macha
authors.forename: Sukhwinder
authors.initials: S
authors.lastname: Kaur
authors.forename: Moorthy P
authors.initials: MP
authors.lastname: Ponnusamy
authors.forename: Parama
authors.initials: P
authors.lastname: Dey
authors.forename: Parthasarathy
authors.initials: P
authors.lastname: Seshacharyulu
authors.forename: Sonny L
authors.initials: SL
authors.lastname: Johansson
authors.forename: Maneesh
authors.initials: M
authors.lastname: Jain
authors.forename: Kay-Uwe
authors.initials: KU
authors.lastname: Wagner
authors.forename: Surinder K
authors.initials: SK
authors.lastname: Batra
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009077:Mucins / Q000096:biosynthesis* / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D009077:Mucins; D012333:RNA, Messenger