Zeps N, Bentel J M, Papadimitriou J M, D'Antuono M F, Dawkins H J
Department of Surgery, University of Western Australia, Queen Elizabeth II Medical Center, Nedlands, Australia.
Differentiation. 1998 Mar;62(5):221-6. doi: 10.1046/j.1432-0436.1998.6250221.x.
The mouse mammary gland undergoes rapid proliferation during puberty, then cyclical proliferation and involution during adulthood within a 5-day estrous cycle. Although proliferation of mammary epithelial cells is directed by elevated serum levels of estrogen acting via the estrogen receptor (ER), the ER status of the proliferating cells remains unknown. We examined the ER expression of proliferating epithelial cell types during pubertal development and normal adult growth using simultaneous immunohistochemistry for ER and tritiated thymidine (3H-Tdr) autoradiography. These studies demonstrate that during pubertal growth (4-6 weeks) ER-negative cells comprise more than 50% of the epithelial cell populations in the terminal end buds (TEBs) and ducts. Furthermore, the majority of proliferating cells in both TEBs and ducts are ER-negative. These findings indicate that proliferation of cells within both the TEBs and the mammary ducts contribute to pubertal growth of the mammary gland and that the greater proportion of dividing cells are ER-negative. Similar patterns of cell growth were observed in the normal estrous cycle when the majority of dividing cells were ER-negative during both pro-estrous and estrous. Intensive labelling of cells with 3H-Tdr was used to identify long-lived mammary epithelial cells which retained 3H-Tdr 2 weeks following labelling (i.e., following 3 estrous cycles). Of the small number of mammary epithelial cells retaining 3H-Tdr label, most were ER-positive luminal cells and only a few were ER-negative basal cells. This study indicates that pubertal growth of the mammary gland comprises division of ER-negative cap cells and of both ER-negative and ER-positive cells in the body of the TEBs and elongating mammary ducts. Similarly, estrogen-driven proliferation of ER-negative and ER-positive luminal cells and ER-negative basal cells maintains the differentiated mammary gland in the adult mouse.
小鼠乳腺在青春期经历快速增殖，然后在成年期的5天发情周期内经历周期性增殖和退化。尽管乳腺上皮细胞的增殖是由通过雌激素受体（ER）起作用的血清雌激素水平升高所引导的，但增殖细胞的ER状态仍然未知。我们使用ER和氚化胸腺嘧啶核苷（3H-Tdr）放射自显影的同步免疫组织化学方法，研究了青春期发育和正常成年生长过程中增殖上皮细胞类型的ER表达。这些研究表明，在青春期生长（4-6周）期间，ER阴性细胞占末端终芽（TEB）和导管中上皮细胞群体的50%以上。此外，TEB和导管中的大多数增殖细胞都是ER阴性。这些发现表明，TEB和乳腺导管内的细胞增殖都有助于乳腺的青春期生长，并且分裂细胞中较大比例是ER阴性。在正常发情周期中观察到类似的细胞生长模式，即在动情前期和发情期，大多数分裂细胞都是ER阴性。用3H-Tdr对细胞进行密集标记，以鉴定在标记后2周（即3个发情周期后）仍保留3H-Tdr的长寿乳腺上皮细胞。在保留3H-Tdr标记的少量乳腺上皮细胞中，大多数是ER阳性的管腔细胞，只有少数是ER阴性的基底细胞。这项研究表明，乳腺的青春期生长包括ER阴性帽细胞以及TEB主体和延长乳腺导管中ER阴性和ER阳性细胞的分裂。同样，雌激素驱动的ER阴性和ER阳性管腔细胞以及ER阴性基底细胞的增殖维持了成年小鼠分化的乳腺。
