Krajewski S, Bodrug S, Krajewska M, Shabaik A, Gascoyne R, Berean K, Reed J C
La Jolla Cancer Research Foundation, Cancer Research Center, CA 92037, USA.
Am J Pathol. 1995 Jun;146(6):1309-19.
The mcl-1 gene encodes an approximately 37-kd protein that has significant homology with Bcl-2, an inhibitor of programmed cell death that is expressed in many types of long-lived cells. In this study we determined the in vivo patterns of Mcl-1 protein production in normal human tissues by immunohistochemical means, using specific polyclonal antisera, and made comparisons with Bcl-2. Like Bcl-2, Mcl-1 immunostaining was observed in epithelial cells in a variety of tissues, including prostate, breast, endometrium, epidermis, stomach, intestine, colon, and respiratory tract. However, often the expression of mcl-1 and bcl-2 in complex epithelia occurred in gradients with opposing directions, such that Bcl-2 immunostaining tended to be higher in the less differentiated cells lining the basement membrane, whereas Mcl-1 immunostaining was more intense in the differentiated cells located in the upper layers of these epithelia. The in vivo patterns of mcl-1 and bcl-2 expression were also strikingly different in several other tissues as well. Within the secondary follicles of lymph nodes and tonsils, for example, germinal center lymphocytes were Mcl-1 positive but mostly lacked Bcl-2; whereas mantle zone lymphocytes expressed bcl-2 but not mcl-1. Intense Mcl-1 immunoreactivity was also detected in several types of neuroendocrine cells, including the adrenal cortical cells that are Bcl-2 negative, sympathetic neurons that also contain Bcl-2, a subpopulation of cells in the pancreatic islets, Leydig cells of the testis, and granulosa lutein cells of the ovarian corpus luteum but not in thyroid epithelium, which is strongly Bcl-2 positive. Little or no Mcl-1 was detected in neurons in the brain and spinal cord, in contrast to Bcl-2, which is present in several types of central nervous system neurons. Conversely, strong Mcl-1 immunostaining was found in cardiac and skeletal muscle, which contain comparatively less Bcl-2. Additional types of cells that are Bcl-2-negative but that expressed mcl-1 include chondrocytes and hepatocytes. These findings demonstrate that mcl-1 expression is widespread in vivo and imply that the Mcl-1 and Bcl-2 proteins fulfill different roles in the overall physiology of cell death regulation.
mcl - 1基因编码一种约37kd的蛋白质，该蛋白质与Bcl - 2具有显著同源性，Bcl - 2是一种程序性细胞死亡抑制剂，在多种长寿细胞类型中表达。在本研究中，我们使用特异性多克隆抗血清，通过免疫组织化学方法确定了正常人组织中Mcl - 1蛋白产生的体内模式，并与Bcl - 2进行了比较。与Bcl - 2一样，在多种组织的上皮细胞中观察到Mcl - 1免疫染色，包括前列腺、乳腺、子宫内膜、表皮、胃、小肠、结肠和呼吸道。然而，在复杂上皮中，mcl - 1和bcl - 2的表达通常呈相反方向的梯度变化，使得Bcl - 2免疫染色在基底膜内衬的分化程度较低的细胞中往往较高，而Mcl - 1免疫染色在这些上皮上层的分化细胞中更强。mcl - 1和bcl - 2表达的体内模式在其他几种组织中也有显著差异。例如，在淋巴结和扁桃体的次级滤泡内，生发中心淋巴细胞Mcl - 1呈阳性，但大多缺乏Bcl - 2；而套区淋巴细胞表达bcl - 2但不表达mcl - 1。在几种神经内分泌细胞中也检测到强烈的Mcl - 1免疫反应性，包括Bcl - 2阴性的肾上腺皮质细胞、也含有Bcl - 2的交感神经元、胰岛中的一部分细胞、睾丸的间质细胞和卵巢黄体的颗粒黄体细胞，但在Bcl - 2强阳性的甲状腺上皮中未检测到。与存在于几种中枢神经系统神经元中的Bcl - 2相反，在脑和脊髓的神经元中几乎未检测到Mcl - 1。相反，在心肌和骨骼肌中发现了强烈的Mcl - 1免疫染色，而这些组织中Bcl - 2含量相对较少。其他Bcl - 2阴性但表达mcl - 1的细胞类型包括软骨细胞和肝细胞。这些发现表明mcl - 1表达在体内广泛存在，并暗示Mcl - 1和Bcl - 2蛋白在细胞死亡调控的整体生理学中发挥不同作用。
