Epitope Characterization of an Aromatase Monoclonal Antibody Suitable for the Assessment of Intratumoral Aromatase Activity

被引：27

作者：

Hong, Yanyan ^{[1
]}

Li, Hongzhi ^{[3
]}

Ye, Jingjing ^{[1
]}

Miki, Yasuhiro ^{[2
]}

Yuan, Yate-Ching ^{[3
]}

Sasano, Hironobu ^{[2
]}

Evans, Dean B. ^{[4
]}

Chen, Shiuan ^{[1
]}

机构：

[1] Beckman Res Inst City Hope, Div Tumor Cell Biol, Duarte, CA USA

[2] Tohoku Univ, Grad Sch Med, Dept Pathol, Aoba Ku, Sendai, Miyagi 980, Japan

[3] Beckman Res Inst City Hope, Div Informat Sci, Duarte, CA USA

[4] Novartis Pharma Ag, Novartis Inst Biomed Res, Oncol Res, Zurich, Switzerland

来源：

PLOS ONE | 2009年 / 4卷 / 11期

基金：

美国国家卫生研究院;

关键词：

SITE-DIRECTED MUTAGENESIS; HUMAN BREAST; ELECTROSTATIC INTERACTIONS; BINDING DOMAIN; REDUCTASE; ESTROGEN; IMMUNOHISTOCHEMISTRY; CYTOCHROME-P-450; VALIDATION; INHIBITION;

D O I：

10.1371/journal.pone.0008050

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Immunohistochemistry is one of the most suitable methods for the detection of intratumoral aromatase in order to identify patients who may respond to aromatase inhibitor therapy in hormone-dependent breast cancer. Previous studies showed statistically significant correlation between results of immnuohistochemistry and biochemical analysis in carcinoma components stained by aromatase monoclonal antibody 677. In this study, determination of the antigenic peptides recognized by aromatase antibodies through epitope mapping, combined with the new knowledge on aromatase-reductase interaction, provide insights for understanding various immunostaining patterns using different aromatase antibodies. Our studies on aromatase-reductase interaction also provided critical information on how aromatase and reductase interact with each other on the endoplasmic reticulum membrane, and identified key residues, including K108 of aromatase, that are involved in the interaction with reductase. Through epitope mapping and taking into consideration the interference with aromatase immunohistochemical staining by NADPH-cytochrome P450 reductase, we demonstrated that monoclonal antibody 677 is a suitable antibody for an assessment of intratumoral aromatase activity in breast cancer patients for making clinical management decisions. These results also provide valuable information to identify new aromatase antibodies for immunohistochemical diagnosis of hormone-dependent breast cancer in future.

引用

页数：10

共 30 条

[1]

BERNHARDT R, 1987, BIOCHEM INT, V14, P823

[2]

BERNHARDT R, 1988, BIOMED BIOCHIM ACTA, V47, P581

[3] CORRELATION OF BREAST-TUMOR AROMATASE-ACTIVITY AND RESPONSE TO AROMATASE INHIBITION WITH AMINOGLUTETHIMIDE [J].

BEZWODA, WR ;

MANSOOR, N ;

DANSEY, R .

ONCOLOGY, 1987, 44 (06) :345-349

[4] A LINK BETWEEN BREAST-CANCER AND LOCAL ESTROGEN BIOSYNTHESIS SUGGESTED BY QUANTIFICATION OF BREAST ADIPOSE-TISSUE AROMATASE CYTOCHROME-P450 TRANSCRIPTS USING COMPETITIVE POLYMERASE CHAIN-REACTION AFTER REVERSE TRANSCRIPTION [J].

BULUN, SE ;

PRICE, TM ;

AITKEN, J ;

MAHENDROO, MS ;

SIMPSON, ER .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1993, 77 (06) :1622-1628

[5]

ESTEBAN JM, 1992, AM J PATHOL, V140, P337

[6] Structural basis for androgen specificity and oestrogen synthesis in human aromatase [J].

Ghosh, Debashis ;

Griswold, Jennifer ;

Erman, Mary ;

Pangborn, Walter .

NATURE, 2009, 457 (7226) :219-U119

[7] Structure and Function of an NADPH-Cytochrome P450 Oxidoreductase in an Open Conformation Capable of Reducing Cytochrome P450 [J].

Hamdane, Djemel ;

Xia, Chuanwu ;

Im, Sang-Choul ;

Zhang, Haoming ;

Kim, Jung-Ja P. ;

Waskell, Lucy .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (17) :11374-11384

[8] Molecular basis for the aromatization reaction and exemestane-mediated irreversible inhibition of human aromatase [J].

Hong, Yanyan ;

Yu, Bin ;

Sherman, Mark ;

Yuan, Yate-Ching ;

Zhou, Dujin ;

Chen, Shiuan .

MOLECULAR ENDOCRINOLOGY, 2007, 21 (02) :401-414

[9] Molecular Characterization of Aromatase [J].

Hong, Yanyan ;

Li, Hongzhi ;

Yuan, Yate-Ching ;

Chen, Shiuan .

STEROID ENZYMES AND CANCER, 2009, 1155 :112-120

[10]

JAMES V H T, 1987, Steroids, V50, P269, DOI 10.1016/0039-128X(83)90077-6

← 1 2 3 →