4S ESTROGEN-RECEPTOR ISOFORMS AND THEIR DISTRIBUTION IN BREAST-CANCER SAMPLES

被引:14
作者
MARSIGLIANTE, S
BAKER, VA
PUDDEFOOT, J
BARKER, S
VINSON, GP
机构
[1] UNIV LONDON, QUEEN MARY & WESTFIELD COLL,FAC BASIC MED SCI, DEPT BIOCHEM,MILE END RD, LONDON E1 4NS, ENGLAND
[2] UNIV LECCE, DIPARTMENTO BIOL, I-73100 LECCE, ITALY
关键词
D O I
10.1677/jme.0.0070205
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The variability in the profile of oestrogen receptor (ER) isoforms in breast tumours has been studied. Using low-resolution isoelectric focussing (IEF), two major ER isoforms with isoelectric point (pI) values of 6.1 and 6.6 could be identified, with corresponding sedimentation coefficients in sucrose density gradients of 8 S and 4 S respectively. Using high-resolution IEF or immunoblotting, the pl 6.6 form (4 S) was shown to be composed of three different species, with pI values of 6.3, 6.6 and 6.8, while the oligomeric pI 6.1 protein (8 S) did not show charge heterogeneity. Data were obtained on the soluble receptors from supernatants of 42 ER-positive primary breast tumour homogenates using high-resolution IEF to obtain ER isoform profiles. It was found that 54.7% of tumours contained the isoforms at pI 6.6 and 6.1, while only 11.9% contained the full complement of isoforms (pl 6.1, 6.3, 6.6 and 6.8). Of the tumours studied, 11.9% contained isoforms of pI 6.1, 6.6 and 6.8, with 14.3% containing isoforms with pl 6.1, 6.6 and 6.3. Very few tumours contained only one isoform, with 4.8% of tumours containing a single isoform at pI 6.1 and 2.4% of tumours containing only the isoform at pI 6.6. All four ER isoforms were also shown to be present in some tumours by immunoblotting using antibody H222 and, in addition, high-resolution IEF indicated that all isoforms bind oestradiol, diethylstilboestrol and tamoxifen, The variability in the ER isoform profile may have a bearing on the known variability of tumour response to endocrine therapy and prognosis.
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页码:205 / 211
页数:7
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