THE NATURE AND SIGNIFICANCE OF MULTIPLE ISOFORMS OF THE ESTROGEN-RECEPTOR IN BREAST-TUMORS

被引:9
作者
PUDDEFOOT, JR
BAKER, VA
BAKKERS, B
MARSIGLIANTE, S
BARKER, S
PANAHY, C
GOODE, AW
CARPENTER, R
VINSON, GP
机构
[1] UNIV LECCE, DIPARTIMENTO BIOL, FISIOL GEN LAB, I-73100 LECCE, ITALY
[2] LISTER HOSP, SURG UNIT, STEVENAGE SG1 4AB, HERTS, ENGLAND
[3] ROYAL LONDON HOSP, SURG UNIT, LONDON E1 1BB, ENGLAND
[4] ST BARTHOLOMEWS HOSP, SURG UNIT, LONDON EC1A 7BE, ENGLAND
关键词
D O I
10.1677/jme.0.0110083
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Oestrogen receptors (ERs) in breast tumours are highly heterogeneous. In previous studies we have shown that at least four isoforms may exist. These migrate in isoelectric focusing (IEF) gels to isoelectric points (pI values) 6.1, 6.3, 6.6 and 6.8. Of these the first (pI 6.1) corresponds to the 8S isoform as detected by sucrose gradient fractionation, while the others all sediment at 4S. In a series of 66 breast tumours it was found that those at pI 6.3 and pI 6.8 were significantly correlated with the presence of progesterone receptors. To characterize the isoforms more fully, ER isoforms labelled by [H-3]oestradiol binding were fractionated by IEF. The results were compared with those obtained after sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting using the H222 anti-ER monoclonal antibody. In other experiments, tumour ER isoforms were covalently labelled with [ring-H-3] tamoxifen aziridine and separated by IEF. The individual isoforms were electroeluted from the IEF gel and further analysed by SDS-PAGE and non-denaturing PAGE. In summary, the evidence shows that the isoforms of pl values 6.3, 6.8 and 6.6 have molecular masses of 50, 65 and 70 kDa respectively. In addition, all three of these isoforms, i.e. the pI 6.3, 6.8 and 6.6 isoforms, could form dimers. We conclude that the three isoforms sedimenting at 4S have the capacity to form dimers and thus may have the potential for binding to oestrogen response elements in the genome.
引用
收藏
页码:83 / 90
页数:8
相关论文
共 32 条
[1]   CHARGE HETEROGENEITY OF HUMAN MAMMARY-TUMOR ESTROGEN-RECEPTORS - RELATIONSHIP WITH A HORMONAL SENSITIVITY TUMOR-MARKER [J].
BAILLEUL, S ;
GAUDUCHON, P ;
MALAS, JP ;
LECHEVREL, C ;
ROUSSEL, G ;
GOUSSARD, J .
CANCER LETTERS, 1988, 40 (03) :299-307
[2]   ESTROGEN-RECEPTOR ISOFORMS, THEIR DISTRIBUTION AND RELATION TO PROGESTERONE-RECEPTOR LEVELS IN BREAST-CANCER SAMPLES [J].
BAKER, VA ;
PUDDEFOOT, JR ;
MARSIGLIANTE, S ;
BARKER, S ;
GOODE, AW ;
VINSON, GP .
BRITISH JOURNAL OF CANCER, 1992, 66 (06) :1083-1087
[3]   A PROTEASE ACTING ON THE ESTROGEN-RECEPTOR MAY MODIFY ITS ACTION IN THE ADULT-RABBIT EPIDIDYMIS [J].
DANZO, BJ .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1986, 25 (04) :511-519
[4]   DISSIMILARITIES BETWEEN THE UTERINE ESTROGEN-RECEPTOR IN CYTOSOL OF CASTRATED AND ESTRADIOL-TREATED RATS [J].
FAYE, JC ;
FARGIN, A ;
BAYARD, F .
ENDOCRINOLOGY, 1986, 118 (06) :2276-2283
[5]  
GREEN S, 1991, NUCL HORMONE RECEPTO, P15
[6]  
Hames B. D., 1990, GEL ELECTROPHORESIS, P1
[7]   ESTRADIOL-STIMULATED PROTEOLYTIC CLEAVAGE OF THE ESTROGEN-RECEPTOR IN MOUSE UTERUS [J].
HORIGOME, T ;
OGATA, F ;
GOLDING, TS ;
KORACH, KS .
ENDOCRINOLOGY, 1988, 123 (05) :2540-2548
[8]   UNIQUE MOLECULAR-PROPERTIES OF A UREA-STABLE AND SALT-STABLE DNA-BINDING ESTROGEN-RECEPTOR DIMER COVALENTLY LABELED WITH THE ANTIESTROGEN [H-3] DESMETHYLNAFOXIDINE AZIRIDINE - A COMPARISON WITH THE ESTROGEN-RECEPTOR COMPLEX [J].
HUTCHENS, TW ;
MCNAUGHT, RW ;
YIP, TT ;
SUZUKI, T ;
LI, CM ;
BESCH, PK .
MOLECULAR ENDOCRINOLOGY, 1990, 4 (02) :255-267
[9]   THYROID-HORMONE RECEPTOR-ALPHA ISOFORMS GENERATED BY ALTERNATIVE SPLICING DIFFERENTIALLY ACTIVATE MYOSIN HC GENE-TRANSCRIPTION [J].
IZUMO, S ;
MAHDAVI, V .
NATURE, 1988, 334 (6182) :539-542
[10]   COMMON NON-HORMONE BINDING-COMPONENT IN NON-TRANSFORMED CHICK OVIDUCT RECEPTORS OF 4 STEROID-HORMONES [J].
JOAB, I ;
RADANYI, C ;
RENOIR, M ;
BUCHOU, T ;
CATELLI, MG ;
BINART, N ;
MESTER, J ;
BAULIEU, EE .
NATURE, 1984, 308 (5962) :850-853