Promotion of estrogen-induced mammary gland carcinogenesis by androgen in the male Noble rat: probable mediation by steroid receptors
Promotion of estrogen-induced mammary gland carcinogenesis by androgen in the male Noble rat: probable mediation by steroid receptors
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DOI：
10.1093/carcin/19.12.2173
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发表时间：
1998-12-01
期刊：
影响因子：
4.7
通讯作者：
Li, SA
中科院分区：
文献类型：
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作者：
Liao, DZJ;Pantazis, CG;Li, SA
内源性和外源性雌激素暴露均与乳腺癌风险增加有关。在一些研究中，血清睾酮水平升高也与乳腺癌风险增加有关。雌激素单独或与孕激素联合可在多种品系的雄性和雌性大鼠中诱发较高的乳腺肿瘤发病率。在雄性诺布尔大鼠中，经17β - 雌二醇（E - 2）和丙酸睾酮（TP）处理后诱发了乳腺导管腺癌。处理8 - 9个月后肿瘤发病率为100%。在这段时间内，单独暴露于雌激素或雄激素均未检测到此类肿瘤。单独使用TP会导致乳腺导管破坏和间质组织增生，而单独使用E - 2会诱导导管上皮生长和结节性非典型增生。为了研究这些激素在乳腺肿瘤发生中的相互作用，对诺布尔大鼠乳腺中的性激素受体进行了表征。在年龄匹配的未处理乳腺上皮中检测到雌激素受体 - α（ER）；在E - 2和E - 2 + TP处理后出现的大多数早期非典型增生病变中以及在E - 2 + TP诱发的乳腺肿瘤中均检测到。在E - 2和E - 2 + TP处理的乳腺以及诱发的肿瘤中检测到两种主要的ER假定异构体，分子量分别为116和120 kDa。在未处理和TP处理的乳腺以及诱发的肿瘤中发现一种54 kDa的ER蛋白。在所有E - 2 + TP诱发的乳腺肿瘤中，孕激素受体 - B（PR - B）和PR - A2以及雄激素受体 - B（AR - B）和AR - A异构体均显著升高。然而，在E - 2和E - 2 + TP处理的雄性大鼠乳腺中，PR和AR的水平都非常低。在E - 2和E - 2 + TP处理的乳腺所诱发的大多数非典型增生病变中，分别检测到低水平和中等水平的AR和PR。这些结果表明，在E - 2 + TP诱发的乳腺和肿瘤中，雄激素可能与AR或PR，或许与这两种受体相互作用，从而影响潜伏期缩短、肿瘤增大，并使发病率提高到100%。
Both endogenous and exogenous estrogen exposure is associated with an increased breast cancer risk. In some studies, elevated serum testosterone levels have also been linked to an increased breast cancer risk. Estrogen alone or combined with progesterone induces high mammary tumor incidences in various strains of both male and female rats. Mammary gland ductal adenocarcinomas were induced after 17 beta-estradiol (E-2) and testosterone propionate (TP) treatment in male Noble rats. Tumor incidence was 100% after 8-9 months of treatment. Such neoplasms were not detected after either estrogen or androgen exposure alone within this time period. TP alone caused disruption of mammary gland ducts and proliferation of stromal tissue, while E-2 treatment alone induced both ductal epithelial growth and nodular atypical hyperplasia, To study the interaction of these hormones in mammary tumorigenesis, sex hormone receptors were characterized in mammary glands of Noble rats. Estrogen receptor-alpha (ER) was detected in age-matched, untreated mammary gland epithelium; in most early atypical hyperplastic lesions appearing after E-2 and E-2 + TP treatment and in E-2 + TP-induced mammary tumors. Two major ER putative isoforms, 116 and 120 kDa, were detected in E-2- and E-2 + TP-treated mammary glands, and in the induced tumors. A 54 kDa ER protein was found in untreated and TP-treated mammary glands, and in the induced tumors. Both progesterone receptor-B (PR-B) and PR-A2, as well as androgen receptor-B (AR-B) and AR-A isoforms were markedly elevated in all E-2 + TP-induced mammary tumors. However, the levels of both PR and AR were very low in mammary glands of E-2- and E-2 + TP-treated male rats. Low and moderate levels of AR and PR, respectively, were detected in most atypical hyperplastic lesions induced by E-2- and E-2 + TP-treated mammary glands. These results suggest that androgens may interact with either AR or PR, and perhaps both receptors, in E-2 + TP-induced mammary glands and the induced tumors to effect the reduction in latency period, enhance tumor size, and increase incidence to 100%.