Durocher F, Simard J, Ouellette J, Richard V, Labrie F, Pelletier G
Lab. of Familial Cancers, CHUL Research Center, Quebec City, Canada.
J Histochem Cytochem. 1997 Sep;45(9):1173-88. doi: 10.1177/002215549704500901.
The breast and ovarian cancer susceptibility gene BRCA1 encodes a phosphoprotein of 1863 amino acids containing a highly conserved N-terminal RING finger domain and a C-terminal acidic region typical of several transcription factors. BRCA1 acts as a tumor suppressor that may inhibit the proliferation of breast and ovarian cancer cells. To gain knowledge and to further understand the biological function of BRCA1, we examined its localization and expression in various tissues from 20-year-old male and female cynomolgus monkeys (Macaca fascicularis) by in situ hybridization using a 35S-labeled human BRCA1 DNA probe fragment derived from exon 11. In mammary glands, BRCA1 expression was primarily located in the duct and acinar epithelial cells. In the ovary, strong BRCA1 expression was detected in granulosa cells in maturing follicles and in luteal cells of the corpus luteum, as well as in the epithelial cells overlying the tunica albuginea. Specific signal was also observed in epithelial cells of the oviduct, endometrium, cervix, and vagina. Moreover, BRCA1 was strongly expressed in the germinal epithelium of the seminiferous tubules as well as over interstitial cells of the testis, in the epithelium of the epididymis, and in epithelial cells bordering the glandular lumen of the seminal vesicles. Signal was also detected in both the anterior and posterior lobes of the pituitary. In the adrenal glands, the signal was greater in the zona glomerulosa compared to the two other cortical zones, whereas the medullary cells were weakly labeled. In the stomach, and in small and large intestine, epithelial cells of the crypts usually exhibited stronger positive reaction than that observed over surface epithelial lining cells. BRCA1 expression was also found in diverse types of epithelial cells of the thyroid, pancreas, salivary glands, trachea, urinary bladder, and kidneys. In addition to demonstrating widespread tissue- and cell-specific expression of the BRCA1 gene in primate tissues, primarily in the epithelia, we observed a weaker but specific signal in various other cell types, suggesting a generalized biological function of BRCA1.
乳腺癌和卵巢癌易感基因BRCA1编码一种由1863个氨基酸组成的磷蛋白，该蛋白含有一个高度保守的N端环指结构域和一个C端酸性区域，这是几种转录因子所特有的。BRCA1作为一种肿瘤抑制因子，可能抑制乳腺癌和卵巢癌细胞的增殖。为了深入了解BRCA1的生物学功能，我们使用来自第11外显子的35S标记的人BRCA1 DNA探针片段，通过原位杂交技术检测了20岁雄性和雌性食蟹猴（猕猴）各种组织中BRCA1的定位和表达。在乳腺中，BRCA1表达主要位于导管和腺泡上皮细胞。在卵巢中，在成熟卵泡的颗粒细胞、黄体的黄体细胞以及白膜上层的上皮细胞中检测到强烈的BRCA1表达。在输卵管、子宫内膜、子宫颈和阴道的上皮细胞中也观察到特异性信号。此外，BRCA1在生精小管的生发上皮以及睾丸间质细胞、附睾上皮和精囊腺腔边界的上皮细胞中强烈表达。在垂体的前叶和后叶也检测到信号。在肾上腺中，与其他两个皮质区相比，球状带的信号更强，而髓质细胞的标记较弱。在胃以及小肠和大肠中，隐窝的上皮细胞通常比表面上皮衬里细胞表现出更强的阳性反应。在甲状腺、胰腺、唾液腺、气管、膀胱和肾脏的各种上皮细胞中也发现了BRCA1表达。除了证明BRCA1基因在灵长类组织中广泛的组织和细胞特异性表达，主要在上皮细胞中，我们还在各种其他细胞类型中观察到较弱但特异性的信号，这表明BRCA1具有广泛的生物学功能。
