Altered protein expression at early-stage rat hepatic neoplasia

Qilie Luo, Linda Siconolfi-Baez, Pallavi Annamaneni, Mark T. Bielawski, Phyllis M. Novikoff, Ruth Hogue Angeletti

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Protein expression patterns were analyzed in a rat model of hepatic neoplasia to detect changes reflecting biological mechanism or potential therapeutic targets. The rat resistant hepatocyte model of carcinogenesis was studied, with a focus on the earliest preneoplastic lesion visible in the liver, the preneoplastic hyperplastic nodule. Expression differences were shown by two-dimensional polyacrylamide gel electrophoresis and image analysis. Polypeptide masses were measured by peptide mass finger-printing using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) and their sequences were obtained by tandem mass spectrometry. Alterations in expression of cytoskeletal and functional proteins were demonstrated, consistent with biological changes known to occur in the preneoplastic cells. Of particular interest was the differential expression of a serine protease inhibitor (serpin) with a role implicated in angiogenesis. Serpin, implicated in the inhibition of angiogenesis, is present in normal liver but has greatly reduced expression at the preneoplastic stage of liver cancer development. Immunofluorescence microscopy with antibodies to this serpin, kallistatin, supports the proteomic identification. Immunofluorescence microscopy with antibodies to the blood vessel marker von Willebrand factor provides evidence for neovascularization in the liver containing multiple preneoplastic nodules. These observations suggest that at an early stage of liver carcinogenesis reduction or loss of angiogenesis inhibitors may contribute to initiation of neoangiogenesis. A number of other identified proteins known to be associated with hepatomas are also present at early-stage neoplasia.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume292
Issue number5
DOIs
StatePublished - May 2007

Fingerprint

Liver
Serine Proteinase Inhibitors
Neoplasms
Proteins
Fluorescence Microscopy
Carcinogenesis
Serpins
Printing
Peptides
Angiogenesis Inhibitors
Cytoskeletal Proteins
Antibodies
Electrophoresis, Gel, Two-Dimensional
von Willebrand Factor
Liver Neoplasms
Tandem Mass Spectrometry
Proteomics
Fingers
Blood Vessels
Hepatocytes

Keywords

  • Angiogenesis
  • Differentially expressed proteins
  • Hepatoma
  • Liver
  • Preneoplastic nodules

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Luo, Q., Siconolfi-Baez, L., Annamaneni, P., Bielawski, M. T., Novikoff, P. M., & Angeletti, R. H. (2007). Altered protein expression at early-stage rat hepatic neoplasia. American Journal of Physiology - Gastrointestinal and Liver Physiology, 292(5). https://doi.org/10.1152/ajpgi.00474.2006

Altered protein expression at early-stage rat hepatic neoplasia. / Luo, Qilie; Siconolfi-Baez, Linda; Annamaneni, Pallavi; Bielawski, Mark T.; Novikoff, Phyllis M.; Angeletti, Ruth Hogue.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 292, No. 5, 05.2007.

Research output: Contribution to journalArticle

Luo, Qilie ; Siconolfi-Baez, Linda ; Annamaneni, Pallavi ; Bielawski, Mark T. ; Novikoff, Phyllis M. ; Angeletti, Ruth Hogue. / Altered protein expression at early-stage rat hepatic neoplasia. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2007 ; Vol. 292, No. 5.
@article{4a8e0ef4c133482aba36c6a81f1c6440,
title = "Altered protein expression at early-stage rat hepatic neoplasia",
abstract = "Protein expression patterns were analyzed in a rat model of hepatic neoplasia to detect changes reflecting biological mechanism or potential therapeutic targets. The rat resistant hepatocyte model of carcinogenesis was studied, with a focus on the earliest preneoplastic lesion visible in the liver, the preneoplastic hyperplastic nodule. Expression differences were shown by two-dimensional polyacrylamide gel electrophoresis and image analysis. Polypeptide masses were measured by peptide mass finger-printing using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) and their sequences were obtained by tandem mass spectrometry. Alterations in expression of cytoskeletal and functional proteins were demonstrated, consistent with biological changes known to occur in the preneoplastic cells. Of particular interest was the differential expression of a serine protease inhibitor (serpin) with a role implicated in angiogenesis. Serpin, implicated in the inhibition of angiogenesis, is present in normal liver but has greatly reduced expression at the preneoplastic stage of liver cancer development. Immunofluorescence microscopy with antibodies to this serpin, kallistatin, supports the proteomic identification. Immunofluorescence microscopy with antibodies to the blood vessel marker von Willebrand factor provides evidence for neovascularization in the liver containing multiple preneoplastic nodules. These observations suggest that at an early stage of liver carcinogenesis reduction or loss of angiogenesis inhibitors may contribute to initiation of neoangiogenesis. A number of other identified proteins known to be associated with hepatomas are also present at early-stage neoplasia.",
keywords = "Angiogenesis, Differentially expressed proteins, Hepatoma, Liver, Preneoplastic nodules",
author = "Qilie Luo and Linda Siconolfi-Baez and Pallavi Annamaneni and Bielawski, {Mark T.} and Novikoff, {Phyllis M.} and Angeletti, {Ruth Hogue}",
year = "2007",
month = "5",
doi = "10.1152/ajpgi.00474.2006",
language = "English (US)",
volume = "292",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "5",

}

TY - JOUR

T1 - Altered protein expression at early-stage rat hepatic neoplasia

AU - Luo, Qilie

AU - Siconolfi-Baez, Linda

AU - Annamaneni, Pallavi

AU - Bielawski, Mark T.

AU - Novikoff, Phyllis M.

AU - Angeletti, Ruth Hogue

PY - 2007/5

Y1 - 2007/5

N2 - Protein expression patterns were analyzed in a rat model of hepatic neoplasia to detect changes reflecting biological mechanism or potential therapeutic targets. The rat resistant hepatocyte model of carcinogenesis was studied, with a focus on the earliest preneoplastic lesion visible in the liver, the preneoplastic hyperplastic nodule. Expression differences were shown by two-dimensional polyacrylamide gel electrophoresis and image analysis. Polypeptide masses were measured by peptide mass finger-printing using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) and their sequences were obtained by tandem mass spectrometry. Alterations in expression of cytoskeletal and functional proteins were demonstrated, consistent with biological changes known to occur in the preneoplastic cells. Of particular interest was the differential expression of a serine protease inhibitor (serpin) with a role implicated in angiogenesis. Serpin, implicated in the inhibition of angiogenesis, is present in normal liver but has greatly reduced expression at the preneoplastic stage of liver cancer development. Immunofluorescence microscopy with antibodies to this serpin, kallistatin, supports the proteomic identification. Immunofluorescence microscopy with antibodies to the blood vessel marker von Willebrand factor provides evidence for neovascularization in the liver containing multiple preneoplastic nodules. These observations suggest that at an early stage of liver carcinogenesis reduction or loss of angiogenesis inhibitors may contribute to initiation of neoangiogenesis. A number of other identified proteins known to be associated with hepatomas are also present at early-stage neoplasia.

AB - Protein expression patterns were analyzed in a rat model of hepatic neoplasia to detect changes reflecting biological mechanism or potential therapeutic targets. The rat resistant hepatocyte model of carcinogenesis was studied, with a focus on the earliest preneoplastic lesion visible in the liver, the preneoplastic hyperplastic nodule. Expression differences were shown by two-dimensional polyacrylamide gel electrophoresis and image analysis. Polypeptide masses were measured by peptide mass finger-printing using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) and their sequences were obtained by tandem mass spectrometry. Alterations in expression of cytoskeletal and functional proteins were demonstrated, consistent with biological changes known to occur in the preneoplastic cells. Of particular interest was the differential expression of a serine protease inhibitor (serpin) with a role implicated in angiogenesis. Serpin, implicated in the inhibition of angiogenesis, is present in normal liver but has greatly reduced expression at the preneoplastic stage of liver cancer development. Immunofluorescence microscopy with antibodies to this serpin, kallistatin, supports the proteomic identification. Immunofluorescence microscopy with antibodies to the blood vessel marker von Willebrand factor provides evidence for neovascularization in the liver containing multiple preneoplastic nodules. These observations suggest that at an early stage of liver carcinogenesis reduction or loss of angiogenesis inhibitors may contribute to initiation of neoangiogenesis. A number of other identified proteins known to be associated with hepatomas are also present at early-stage neoplasia.

KW - Angiogenesis

KW - Differentially expressed proteins

KW - Hepatoma

KW - Liver

KW - Preneoplastic nodules

UR - http://www.scopus.com/inward/record.url?scp=34347390866&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34347390866&partnerID=8YFLogxK

U2 - 10.1152/ajpgi.00474.2006

DO - 10.1152/ajpgi.00474.2006

M3 - Article

C2 - 17272515

AN - SCOPUS:34347390866

VL - 292

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 5

ER -