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年龄和产次对 FVB/N-RC 小鼠乳腺病变和祖细胞的影响。

Effects of age and parity on mammary gland lesions and progenitor cells in the FVB/N-RC mice.

机构信息

Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

出版信息

PLoS One. 2012;7(8):e43624. doi: 10.1371/journal.pone.0043624. Epub 2012 Aug 30.

Abstract

The FVB/N mouse strain is extensively used in the development of animal models for breast cancer research. Recently it has been reported that the aging FVB/N mice develop spontaneous mammary lesions and tumors accompanied with abnormalities in the pituitary glands. These observations have a great impact on the mouse models of human breast cancer. We have developed a population of inbred FVB/N mice (designated FVB/N-RC) that have been genetically isolated for 20 years. To study the effects of age and parity on abnormalities of the mammary glands of FVB/N-RC mice, twenty-five nulliparous and multiparous (3-4 pregnancies) females were euthanized at 16-22 months of age. Examination of the mammary glands did not reveal macroscopic evidence of mammary gland tumors in either aged-nulliparous or multiparous FVB/N-RC mice (0/25). However, histological analysis of the mammary glands showed rare focal nodules of squamous changes in 2 of the aged multiparous mice. Mammary gland hyperplasia was detected in 8% and 71% of the aged-nulliparous and aged-multiparous mice, respectively. Epithelial contents and serum levels of triiodothyronine were significantly higher in the experimental groups than the 14-wk-old control mice. Immuno-histochemical staining of the pituitary gland pars distalis showed no difference in prolactin staining between the control and the aged mice. Tissue transplant and dilution studies showed no effect of age and/or parity on the ability of putative progenitor cells present among the injected mammary cells to repopulate a cleared fat pad and develop a full mammary gland outgrowth. This FVB/N-RC mouse substrain is suitable to develop mouse models for breast cancer.

摘要

FVB/N 品系小鼠被广泛用于乳腺癌研究的动物模型开发。最近有报道称,衰老的 FVB/N 小鼠会自发出现乳腺病变和肿瘤,并伴有垂体异常。这些观察结果对人类乳腺癌的小鼠模型有很大影响。我们已经开发了一个近交系 FVB/N 小鼠品系(命名为 FVB/N-RC),该品系已经遗传隔离了 20 年。为了研究年龄和产次对 FVB/N-RC 小鼠乳腺异常的影响,25 只未产和多产(3-4 胎)雌性小鼠在 16-22 月龄时被安乐死。对乳腺的检查未发现衰老的未产和多产 FVB/N-RC 小鼠(0/25)中有乳腺肿瘤的宏观证据。然而,对乳腺的组织学分析显示,2 只衰老的多产小鼠中有罕见的局灶性鳞状细胞结节。在衰老的未产和多产小鼠中,乳腺增生分别检测到 8%和 71%。实验组的乳腺上皮细胞含量和血清三碘甲状腺原氨酸水平明显高于 14 周龄对照组小鼠。垂体远侧部的免疫组织化学染色显示,对照组和衰老组小鼠的催乳素染色没有差异。组织移植和稀释研究表明,年龄和/或产次对注射乳腺细胞中存在的潜在祖细胞的能力没有影响,这些祖细胞可以重新填充清除的脂肪垫并发育出完整的乳腺。这种 FVB/N-RC 小鼠亚系适合开发乳腺癌小鼠模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce26/3431359/76b79c8423aa/pone.0043624.g001.jpg

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