Copper-transporting P-type adenosine triphosphatase (ATP7B) is expressed in human breast carcinoma

Atsuko Kanzaki; Masakazu Toi; Nouri Neamati; Hitoshi Miyashita; Masahiro Oubu; Kentaro Nakayama; Hiroko Bando; Kenji Ogawa; Masato Mutoh; Shiro Mori; Kunihiko Terada; Toshihiro Sugiyama; Manabu Fukumoto; Yuji Takebayashi

doi:10.1111/j.1349-7006.2002.tb01202.x

Copper-transporting P-type adenosine triphosphatase (ATP7B) is expressed in human breast carcinoma

Jpn J Cancer Res. 2002 Jan;93(1):70-7. doi: 10.1111/j.1349-7006.2002.tb01202.x.

Authors

Atsuko Kanzaki¹, Masakazu Toi, Nouri Neamati, Hitoshi Miyashita, Masahiro Oubu, Kentaro Nakayama, Hiroko Bando, Kenji Ogawa, Masato Mutoh, Shiro Mori, Kunihiko Terada, Toshihiro Sugiyama, Manabu Fukumoto, Yuji Takebayashi

Affiliation

¹ Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai 980-8575, Japan. [email protected]

Abstract

This is the first report to show that a copper-transporting P-type adenosine triphosphatase, ATP7B, is expressed in certain breast carcinomas, and a priori knowledge of its expression is important for the choice of therapy. We investigated the hypothesis that ATP7B, which was shown to be associated with cisplatin resistance in vitro, is expressed in certain breast carcinomas. To test this hypothesis, ATP7B expression and protein level were examined in 41 breast carcinomas using RT-PCR and immunohistochemistry. ATP7B gene / protein could be detected in 22.0% (9 / 41) of breast carcinomas and ATP7B gene expression was correlated well with the protein expression. In nine ATP7B-positive tumors, adjacent normal breast tissue was similarly analyzed, revealing that ATP7B is upregulated in breast carcinoma. ATP7B gene expression in poorly differentiated carcinoma was significantly higher than that in well- / moderately differentiated carcinoma (P = 0.012). Furthermore, we found no association between the ATP7B gene / protein expression and that of MDR1, MRP1, LRP and BCRP. These findings suggested that ATP7B gene expression might be a chemoresistance marker for cisplatin in patients with poorly differentiated breast carcinoma.

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters / metabolism
Adenosine Triphosphatases / genetics*
Adenosine Triphosphatases / metabolism
Adult
Aged
Aged, 80 and over
Arabidopsis Proteins*
Base Pair Mismatch
Breast Neoplasms / genetics*
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Carcinoma / genetics*
Carcinoma / metabolism
Carcinoma / pathology
Cation Transport Proteins / genetics*
Cation Transport Proteins / metabolism
Copper-Transporting ATPases
DNA-Binding Proteins / metabolism
Female
Humans
Immunoenzyme Techniques
Middle Aged
Multidrug Resistance-Associated Proteins*
MutS Homolog 3 Protein
Neoplasm Proteins*
Plant Proteins / metabolism
RNA, Messenger / metabolism
Receptors, Estrogen / metabolism
Receptors, Progesterone / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Up-Regulation

Substances

ABCG2 protein, human
ATP Binding Cassette Transporter, Subfamily B, Member 1
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters
Arabidopsis Proteins
Cation Transport Proteins
DNA-Binding Proteins
LRP1 protein, Arabidopsis
MSH3 protein, human
Multidrug Resistance-Associated Proteins
MutS Homolog 3 Protein
Neoplasm Proteins
Plant Proteins
RNA, Messenger
Receptors, Estrogen
Receptors, Progesterone
Adenosine Triphosphatases
ATP7B protein, human
Copper-Transporting ATPases
multidrug resistance-associated protein 1