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
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
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DOI：
10.1210/jc.77.6.1622
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发表时间：
1993-12-01
影响因子：
5.8
通讯作者：
SIMPSON, ER
中科院分区：
文献类型：
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作者：
BULUN, SE;PRICE, TM;SIMPSON, ER
在许多组织中，C-19类固醇被一种特殊形式的细胞色素P450转化为雌激素，即芳香酶细胞色素P450(P450arom)。脂肪组织是绝经后妇女雌激素形成的主要部位。芳香酶活性和P450arom转录本主要存在于脂肪组织的基质细胞成分中。旨在调查乳房脂肪组织中局部芳香酶活性增加是否会影响乳腺癌生长的研究得出了不同的结果。为了澄清这一争议，在切除乳房肿瘤时(n=13)，从四个乳房象限获取脂肪组织。用竞争性聚合酶链式反应定量检测乳房脂肪P450arom信使RNA的表达水平，并与10 mU人脂肪总RNA和1 pg大鼠互补RNA(内标)进行逆转录后进行比较。在13例患者中，有9例(69%)P450arom转录本水平最高位于肿瘤的象限。这种相关性具有统计学意义(P(0.001)。在乳房缩小术(对照组，n=9)中获得的P450arom转录本在无疾病个体的乳房脂肪组织中的区域分布不利于乳房的任何特定区域。我们还通过形态计量学对乳房切除标本中每个象限的脂肪组织样本的组织成分进行了量化。基质细胞的分布与P450arom转录水平的分布显著相关，因为含有与最高转录水平匹配的基质细胞比例最高的象限(P<；0.01)。虽然承载肿瘤的象限含有最高比例的间质细胞，但这种相关性在统计学上并不显著。乳腺肿瘤周围的脂肪组织显示雌激素生物合成增加，这可能促进肿瘤的生长。进一步认为，乳腺脂肪组织中基质细胞成分的分布导致局部P450arom表达升高，这反过来可能有利于乳腺这些易患区域的肿瘤的发展和生长。肿瘤的存在与近端脂肪组织中P450arom水平升高之间的相关性与肿瘤大小、淋巴结转移、组织学类型或分级、雌孕激素受体状态、脱氧核糖核酸指数或S时相比例无关。
C-19 steroids are converted to estrogens in a number of tissues by a specific form of cytochrome P450, namely aromatase cytochrome P450 (P450arom). Adipose tissue is the principal site of estrogen formation in postmenopausal women. Aromatase activity as well as P450arom transcripts primarily reside in the stromal cell component of the adipose tissue. Studies designed to investigate whether increased local aromatase activity in breast adipose tissue influences the growth of breast cancers have yielded discrepant results. In an attempt to clarify this controversy, adipose tissue was obtained from the four breast quadrants at the time of mastectomy (n = 13) performed for removal of a tumor. Breast fat P450arom messenger RNA levels were quantified and compared between the four quadrants within each specimen using competitive polymerase chain reaction after reverse transcription in which 10 mu g human adipose total RNA together with 1 pg rat complementary RNA (internal standard) were reverse transcribed and coamplified.In 9 out of 13 patients (69%), highest P450arom transcript levels colocalized to the quadrants bearing tumors. This correlation was statistically significant (P ( 0.001). The regional distribution of P450arom transcripts in breast adipose tissue of disease-free individuals, obtained during reduction mammoplasty (control group, n = 9), did not favor any particular region of the breast. We also quantified by morphometry the histological components of the adipose tissue samples from each quadrant in mastectomy specimens. The distribution of stromal cells significantly correlated with the distribution of P450arom transcript levels, in that quadrants containing highest proportions of stromal cells matched to highest transcript levels (P < 0.01). Although the quadrants bearing tumors contained the highest percentage of stromal cells, this correlation was not statistically significant.The adipose tissue surrounding a breast tumor displays increased estrogen biosynthesis, which may promote tumor growth. It is further suggested that the distribution of stromal cell components in breast adipose tissue gives rise to locally elevated P450arom expression, which in turn may favor neoplastic development and growth in these predisposed areas of the breast. The correlation between the presence of a tumor and elevated P450arom levels in the proximal adipose tissue is independent of tumor size, node involvement, histological type or grade, estrogen/progesterone receptor status, DNA index, or S-phase fraction.