title: Heterochromatin Protein 1 Binding Protein 3 Expression as a Candidate Marker of Intrinsic 5-Fluorouracil Resistance.
abstract: BACKGROUND
  Despite receiving post-operative 5-fluorouracil (5-FU)-based chemotherapy, approximately 50% of patients with stage IIIC colon cancer experience recurrence. Currently, no molecular signature can predict response to 5-FU.
  
  
  METHODS
  Mouse models of colon cancer have been developed and characterized. Individual tumors in these mice can be longitudinally monitored and assessed to identify differences between those that are responsive and those that are resistant to therapy. Gene expression was analyzed in serial biopsies that were collected before and after treatment with 5-FU. Colon tumors had heterogeneous responses to treatment with 5-FU. Microarray analysis of pre-treatment biopsies revealed that Hp1bp3, a gene encoding heterochromatin protein 1 binding protein 3, was differentially expressed between sensitive and resistant tumors.
  
  
  CONCLUSIONS
  Using mouse models of human colorectal cancer, Hp1bp3 was identified as a candidate marker of intrinsic 5-FU resistance and may represent a potential biomarker for patient stratification or a target of clinical importance.
authors.affiliation: Department of Oncology, K4/532 Clinical Science Center, Madison, WI, U.S.A.
authors.forename: Jamie N
authors.initials: JN
authors.lastname: Hadac
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, K4/532 Clinical Science Center, Madison, WI, U.S.A.
authors.forename: Devon D
authors.initials: DD
authors.lastname: Miller
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, K4/532 Clinical Science Center, Madison, WI, U.S.A.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Grimes
authors.affiliation: Department of Oncology, K4/532 Clinical Science Center, Madison, WI, U.S.A.
authors.forename: Linda
authors.initials: L
authors.lastname: Clipson
authors.affiliation: Departments of Statistics and of Biostatistics and Medical Informatics, 1245a, K6/434 Medical Sciences Center, Madison, WI, U.S.A.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Newton
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, K4/532 Clinical Science Center, Madison, WI, U.S.A.
authors.forename: William R
authors.initials: WR
authors.lastname: Schelman
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, K4/532 Clinical Science Center, Madison, WI, U.S.A. Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, U.S.A. rbhalberg@medicine.wisc.edu.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Halberg
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016264:Dextran Sulfate; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D014408:Biomarkers, Tumor; C000598191:HP1BP3 protein, mouse; D009687:Nuclear Proteins; D016264:Dextran Sulfate; D005472:Fluorouracil
keywords: 5-fluorouracil; Colorectal cancer; chemotherapy; heterochromatin protein 1 binding protein 3; intrinsic resistance; mouse models