通过实时聚合酶链反应对乳腺癌中雌激素受体α和β信使核糖核酸表达进行定量分析。
Quantitative analysis of estrogen receptor-alpha and -beta messenger RNA expression in breast carcinoma by real-time polymerase chain reaction.
作者信息
Iwao K, Miyoshi Y, Egawa C, Ikeda N, Tsukamoto F, Noguchi S
机构信息
Department of Surgical Oncology, Osaka University Medical School, Osaka, Japan.
出版信息
Cancer. 2000 Oct 15;89(8):1732-8. doi: 10.1002/1097-0142(20001015)89:8<1732::AID-CNCR13>3.0.CO;2-2.
BACKGROUND
Estrogen action is mediated not only through a classic estrogen receptor (ER) (ER-alpha) but also through a second ER (ER-beta) that has a structure and function similar to ER-alpha. A correlation between ER-beta mRNA expression with ER and progesterone receptor (PR) protein levels as well as prognostic factors remains to be established in breast carcinoma.
METHODS
The authors conducted a quantitative analysis of ER-alpha and ER-beta mRNA expression in 116 breast tumors using real-time polymerase chain reaction (PCR), and investigated a possible correlation between ER-alpha and ER-beta mRNA expression and ER and PR status as determined by enzyme immunoassay as well as with various prognostic factors.
RESULTS
ER-alpha mRNA levels were significantly (P < 0.01) higher in ER positive compared with ER negative tumors. Conversely, ER-beta mRNA levels were significantly (P < 0.01) lower in ER positive compared with ER negative tumors. Accordingly, the ratio of ER-beta to ER-alpha was significantly (P < 0.01) higher in ER negative compared with ER positive tumors. A subset analysis based on ER and PR status showed that ER-beta mRNA levels as well as the ratios of ER-beta to ER-alpha mRNA level were highest in ER negative and PR negative tumors (P < 0.05). ER-alpha mRNA levels were significantly (P < 0.05) higher in postmenopausal compared with premenopausal tumors. Histologic Grade 3 tumors showed a significant decrease in ER-alpha mRNA levels compared with Grade 1 and 2 tumors (P < 0.01 and P < 0.05, respectively). No significant correlation between ER-alpha and ER-beta mRNA levels and histologic type, tumor size, or lymph node status was observed.
CONCLUSIONS
An absolute and relative increase in ER-beta mRNA levels in ER negative and PR negative breast tumors, which rarely respond to endocrine therapy, suggests the possible involvement of up-regulation of ER-beta mRNA in the development of estrogen-independent tumors.
背景
雌激素作用不仅通过经典雌激素受体（ER）（ER-α）介导，还通过结构和功能与ER-α相似的第二种ER（ER-β）介导。乳腺癌中ER-β mRNA表达与ER和孕激素受体（PR）蛋白水平以及预后因素之间的相关性仍有待确定。
方法
作者采用实时聚合酶链反应（PCR）对116例乳腺肿瘤中的ER-α和ER-β mRNA表达进行定量分析，并研究ER-α和ER-β mRNA表达与酶免疫测定所确定的ER和PR状态以及各种预后因素之间的可能相关性。
结果
与ER阴性肿瘤相比，ER阳性肿瘤中的ER-α mRNA水平显著更高（P < 0.01）。相反，与ER阴性肿瘤相比，ER阳性肿瘤中的ER-β mRNA水平显著更低（P < 0.01）。因此，与ER阳性肿瘤相比，ER阴性肿瘤中ER-β与ER-α的比值显著更高（P < 0.01）。基于ER和PR状态的亚组分析显示，ER-β mRNA水平以及ER-β与ER-α mRNA水平的比值在ER阴性和PR阴性肿瘤中最高（P < 0.05）。与绝经前肿瘤相比，绝经后肿瘤中的ER-α mRNA水平显著更高（P < 0.05）。与1级和2级肿瘤相比，3级组织学肿瘤的ER-α mRNA水平显著降低（分别为P < 0.01和P < 0.05）。未观察到ER-α和ER-β mRNA水平与组织学类型、肿瘤大小或淋巴结状态之间存在显著相关性。
结论
ER阴性和PR阴性乳腺肿瘤中ER-β mRNA水平的绝对和相对增加，这些肿瘤很少对内分泌治疗有反应，提示ER-β mRNA上调可能参与雌激素非依赖性肿瘤的发生发展。
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