Decreased HER-2 tyrosine kinase expression in rectal mucosa of FAP patients following low-dose sulindac chemoprevention

Cancer Lett. 1998 Dec 25;134(2):201-7. doi: 10.1016/s0304-3835(98)00254-7.

Abstract

As a part of the mechanisms of action in reversing FAP adenomas by the low-dose sulindac maintenance therapy (2 x 25 mg/patient per day), the extent of HER-2 proto-oncogene expression in the rectal mucosa seems to be of interest. Immunocytochemical analyses were performed in plasma and in rectal tissue of sulindac-treated FAP patients during an 18 months follow-up and compared with rectal tissue of patients with FAP, Crohn's disease, or rectal cancer or with healthy volunteers. HER-2 was significantly reduced and maintained in tissue under sulindac chemoprevention below base line levels of healthy individuals, but not in plasma. Therefore, a direct or indirect effect of sulindac as a tyrosine kinase inhibitor may be implicated. During NSAID treatment HER-2 protein expression as a prognostic tool seems to be of little clinical relevance.

MeSH terms

  • Adenomatous Polyposis Coli / metabolism*
  • Adenomatous Polyposis Coli / prevention & control*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Case-Control Studies
  • Down-Regulation
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intestinal Mucosa / enzymology*
  • Male
  • Middle Aged
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / biosynthesis*
  • Proto-Oncogene Mas
  • Receptor, ErbB-2 / biosynthesis*
  • Receptor, ErbB-2 / blood
  • Rectum / enzymology*
  • Sulindac / administration & dosage
  • Sulindac / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Enzyme Inhibitors
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Sulindac
  • Protein-Tyrosine Kinases
  • Receptor, ErbB-2