Mutation analysis of copper-transporting P-type adenosine triphosphatase (ATP7B) in human solid carcinomas

Anticancer Res. 2003 Mar-Apr;23(2C):1913-5.

Abstract

A major obstacle in the treatment of human solid carcinomas is the intrinsic/acquired resistance to cisplatin-based chemotherapy. Copper-transporting P-type adenosine triphosphatase (ATP7B) has been reported to be associated with cisplatin resistance in vitro. ATP7B is overexpressed in human solid carcinomas such as breast, gastric and oral squamous cell carcinomas. ATP7B expression has an influential effect on some subsets of patients with cisplatin-treated carcinomas. ATP7B mutation is well-known as a cause of Wilson's disease. In addition, the six copper-binding domain and ATP-binding domain of ATP7B are important for the transportation of metals. Therefore, we performed the mutation analysis at the six copper-binding domain and ATP-binding domain of ATP7B. No mutation at the six copper-binding domain and ATP-binding domain was observed in breast, gastric and oral squameous cell carcinomas. These results indicate that the analysis of the ATP7B gene and/or protein will be helpful for the choice of chemotherapy in patients with human solid carcinomas.

MeSH terms

  • Adenosine Triphosphatases / biosynthesis
  • Adenosine Triphosphatases / genetics*
  • Base Sequence
  • Binding Sites
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Cation Transport Proteins / biosynthesis
  • Cation Transport Proteins / genetics*
  • Copper / metabolism
  • Copper-Transporting ATPases
  • DNA Mutational Analysis
  • Drug Resistance, Neoplasm
  • Humans
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Protein Structure, Tertiary
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism

Substances

  • Cation Transport Proteins
  • Copper
  • Adenosine Triphosphatases
  • ATP7B protein, human
  • Copper-Transporting ATPases