Tissue estradiol is selectively elevated in receptor positive breast cancers while tumour estrone is reduced independent of receptor status

被引:82
作者
Lonning, P. E. [1 ,2 ]
Helle, H. [1 ,2 ]
Duong, N. K. [1 ,2 ]
Ekse, D. [1 ,2 ]
Aas, T. [3 ]
Geisler, J. [1 ,2 ]
机构
[1] Haukeland Hosp, Dept Oncol, Jonas Lies Vei 26, N-5021 Bergen, Norway
[2] Univ Bergen, Inst Med, Sect Oncol, N-5021 Bergen, Norway
[3] Haukeland Hosp, Dept Surg, N-5021 Bergen, Norway
关键词
Breast cancer; Estrogens; Estradiol; Estrone; Estrone sulphate; Aromatase; NONSTEROIDAL AROMATASE INHIBITOR; POSTMENOPAUSAL WOMEN; INTRAMUSCULAR; 4-HYDROXYANDROSTENEDIONE; PERIPHERAL AROMATIZATION; ANASTROZOLE ARIMIDEX; MAMMOGRAPHIC DENSITY; SENSITIVE ASSAY; SEX-HORMONES; BODY-MASS; IN-VIVO;
D O I
10.1016/j.jsbmb.2009.06.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous studies have suggested elevated estrogen production in tumour-bearing breast quadrants as well as in breast cancers versus benign tissue. Using highly sensitive assays, we determined breast cancer tissue estrogen concentrations together with plasma and benign tissue estrogen concentrations in each quadrant obtained from mastectomy specimens (34 postmenopausal and 13 premenopausal women). We detected similar concentrations of each of the three major estrogens estradiol (E-2) estrone (E-1) and E1S in tumour-bearing versus non-tumour-bearing quadrants. Considering malignant tumours, intratumour E-1 levels were reduced in cancer tissue obtained from pre- as well as postmenopausal women independent of tumour ER status (average ratio E, cancer: benign tissue of 0.2 and 0.3, respectively; p < 0.001 for both groups), suggesting intratumour aromatization to be of minor importance. The most striking finding was a significant (4.1-8.6-fold) increased E-2 concentration in ER positive tumours versus normal tissue (p < 0.05 and <0.001 for pre- and postmenopausal patients, respectively), contrasting low E-2 concentrations in ER- tumours (p < 0.01 and <0.001 comparing E-2 levels between ER+ and ER- tumours in pre- and postmenopausals, respectively). A possible explanation to our finding is increased ligand receptor binding capacity for E-2 in receptor positive tumours but alternative factors influencing intratumour estrogen disposition cannot be excluded. (c) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:31 / 41
页数:11
相关论文
共 69 条
[1]   Adiposity, adult weight change, and postmenopausal breast cancer risk [J].
Ahn, Jiyoung ;
Schatzkin, Arthur ;
Lacey, James V., Jr. ;
Albanes, Demetrius ;
Ballard-Barbash, Rachel ;
Adams, Kenneth F. ;
Kipnis, Victor ;
Mouw, Traci ;
Hollenbeck, Albert R. ;
Leitzmann, Michael F. .
ARCHIVES OF INTERNAL MEDICINE, 2007, 167 (19) :2091-2102
[2]   ON THE SIGNIFICANCE OF INSITU PRODUCTION OF ESTROGENS IN HUMAN BREAST-CANCER TISSUE [J].
BLANKENSTEIN, MA ;
MAITIMUSMEELE, I ;
DONKER, GH ;
DAROSZEWSKI, J ;
MILEWICZ, A ;
THIJSSEN, JHH .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1992, 41 (3-8) :891-896
[3]   THE RELATIONSHIP BETWEEN 17-BETA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY AND ESTROGEN CONCENTRATIONS IN HUMAN-BREAST TUMORS AND IN NORMAL BREAST-TISSUE [J].
BONNEY, RC ;
REED, MJ ;
DAVIDSON, K ;
BERANEK, PA ;
JAMES, VHT .
CLINICAL ENDOCRINOLOGY, 1983, 19 (06) :727-739
[4]   Heritability of mammographic density, a risk factor for breast cancer [J].
Boyd, NF ;
Dite, GS ;
Stone, J ;
Gunasekara, A ;
English, DR ;
McCredie, MRE ;
Giles, GG ;
Tritchler, D ;
Chiarelli, A ;
Yaffe, MJ ;
Hopper, JL .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 347 (12) :886-894
[5]   Mammographic density and the risk and detection of breast cancer [J].
Boyd, Norman F. ;
Guo, Helen ;
Martin, Lisa J. ;
Sun, Limei ;
Stone, Jennifer ;
Fishell, Eve ;
Jong, Roberta A. ;
Hislop, Greg ;
Chiarelli, Anna ;
Minkin, Salomon ;
Yaffe, Martin J. .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (03) :227-236
[6]   The human CYP19 (aromatase P450) gene:: update on physiologic roles and genomic organization of promoters [J].
Bulun, SE ;
Sebastian, S ;
Takayama, K ;
Suzuki, T ;
Sasano, H ;
Shozu, M .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2003, 86 (3-5) :219-224
[7]   Prevention of breast cancer in women who carry BRCA1 or BRCA2 mutations:: A critical review of the literature [J].
Calderon-Margalit, R ;
Paltiel, O .
INTERNATIONAL JOURNAL OF CANCER, 2004, 112 (03) :357-364
[8]   Positive and negative transcriptional regulation of aromatase expression in human breast cancer tissue [J].
Chen, S ;
Ye, JJ ;
Kijima, I ;
Kinoshita, Y ;
Zhou, DJ .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2005, 95 (1-5) :17-23
[9]   Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues [J].
Chetrite, GS ;
Cortes-Prieto, J ;
Philippe, JC ;
Wright, F ;
Pasqualini, JR .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2000, 72 (1-2) :23-27
[10]  
deJong PC, 1997, CANCER RES, V57, P2109