McManus M J, Welsch C W
Cancer Res. 1981 Sep;41(9 Pt 1):3300-5.
Five biopsy specimens of morphologically normal human breast tissues, obtained from the margins of five benign human breast tumors, were processed into slices (4.0 x 4.0 x 0.1 mm) and transplanted s.c. dorsally (eight to ten slices/mouse) into forty-three 6- to 8-week-old female BALB/c athymic nude mice. Each individual human breast tissue specimen was transplanted into seven to ten mice. After 30 days, the mice were divided into four groups and treated for 30 days as follows: (a) controls receiving s.c. cholesterol pellets (38 mg); (b) estrogens that were administered in s.c. pellets containing 2 mg 17 beta-estradiol and 38 mg cholesterol and in drinking water containing 0.5 mg estrone per liter; (c) rat pituitary tumor (RPT), a cell suspension of MtT-W10 RPT that secretes large amounts of prolactin and growth hormone, injected dorsorostrally; and (d) RPT plus estrogens. Three to five human breast tissue grafts were removed from each mouse at the onset of treatment, and the remainder were removed at termination of treatment. DNA synthesis in the ductal epithelium was determined in pre- and posttreatment grafts by [3H]thymidine autoradiography after incubation of grafts for 4 hr in an isotope-enriched medium. The labeling index (LI), mean number of labeled epithelial cells per unit area of epithelial tissue, in pre- and posttreatment grafts was, respectively: (a) control, 7.6 +/- 1.4 and 7.1 +/- 1.4; (b) estrogens, 5.5 +/- 0.6 and 17.9 +/- 2.3; (c) RPT, 6.2 +/- 0.7 and 8.0 +/- 1.5; and (d) RPT plus estrogens, 6.3 +/- 0.8 and 26.6 +/- 2.5. A significant increase in LI was observed after treatment with estrogens (p less than 0.05) or RPT plus estrogen (p less than 0.001). Mean LI after treatment with RPT plus estrogens was significantly greater (p less than 0.02) than after estrogens alone. RPT alone did not significantly alter the LI. Thus, these results provide in vivo evidence that estrogens enhance DNA synthesis of the ductal epithelium of the normal human breast and that a growth factor (or factors) from RPT acts synergistically with estrogens to produce a more pronounced increase in DNA synthesis. RPT growth factors (perhaps prolactin and/or growth hormone) appear to require estrogens for DNA synthesis stimulation in normal human breast ductal epithelium.
从五个良性人乳腺肿瘤边缘获取的五份形态学正常的人乳腺组织活检标本，被加工成切片（4.0×4.0×0.1毫米），并背侧皮下移植（每只小鼠八至十片）到四十三只6至8周龄的雌性BALB/c无胸腺裸鼠体内。每份人乳腺组织标本分别移植到七至十只小鼠体内。30天后，将小鼠分为四组，并按如下方式处理30天：（a）对照组皮下植入胆固醇丸剂（38毫克）；（b）雌激素组，皮下植入含2毫克17β-雌二醇和38毫克胆固醇的丸剂，并饮用每升含0.5毫克雌酮的水；（c）大鼠垂体瘤（RPT）组，向背侧头端注射分泌大量催乳素和生长激素的MtT-W10 RPT细胞悬液；（d）RPT加雌激素组。在治疗开始时从每只小鼠身上取出三至五个人乳腺组织移植物，其余的在治疗结束时取出。在富含同位素的培养基中孵育移植物4小时后，通过[3H]胸腺嘧啶核苷放射自显影术测定治疗前后移植物中导管上皮的DNA合成。治疗前后移植物中的标记指数（LI），即上皮组织单位面积内标记上皮细胞的平均数，分别为：（a）对照组，7.6±1.4和7.1±1.4；（b）雌激素组，5.5±0.6和17.9±2.3；（c）RPT组，6.2±0.7和8.0±1.5；（d）RPT加雌激素组，6.3±0.8和26.6±2.5。用雌激素治疗后（p<0.05）或RPT加雌激素治疗后（p<0.001）观察到LI显著增加。RPT加雌激素治疗后的平均LI显著高于单独使用雌激素后（p<0.02）。单独使用RPT并未显著改变LI。因此，这些结果提供了体内证据，表明雌激素可增强正常人乳腺导管上皮的DNA合成，并且来自RPT的一种生长因子（或多种因子）与雌激素协同作用，使DNA合成产生更明显的增加。RPT生长因子（可能是催乳素和/或生长激素）似乎需要雌激素来刺激正常人乳腺导管上皮的DNA合成。
