Garcia M, Lacombe M J, Duplay H, Cavailles V, Derocq D, Delarue J C, Krebs B, Contesso G, Sancho-Garnier H, Richer G
Unité d'Endocrinologie Cellulaire et Moléculaire, INSERM U 148, Montpellier, France.
J Steroid Biochem. 1987;27(1-3):439-45. doi: 10.1016/0022-4731(87)90338-4.
We have previously described a secreted glycoprotein of mol. wt 52,000 (52-kDa protein) which is induced by estrogen in some human breast cancer cell lines. This protein has been identified as the proenzyme of a lysosomal cathepsin-D-like protease which is secreted in large proportions in breast cancer cells. To determine which information may be generated by this marker when detected in mammary tumors, in comparison with hormone receptors, we used monoclonal antibodies interacting specifically with the 52-kDa protein and its related cellular processed products (mols. wts 48 and 34 kDa). A high concentration of this protein has been shown in proliferative ductal mastopathies and cysts, suggesting its value in detecting high-risk mastopathies. We now present the immunoperoxidase distribution of this protein in breast carcinoma compared to the cytosolic hormone receptors assayed in parallel. In 232 breast cancers, no correlation was found between the cellular 52-kDa protein content and cytosolic estrogen or progesterone receptor concentrations. This absence of correlation was also shown by the constitutive production of this protein by estrogen-receptor-negative breast cancer cell lines and confirmed by double immunostaining of breast cancer cell aspirates showing a dissociation between the cytoplasmic staining of this 52-kDa lysosomal protease and the nuclear staining of the estrogen receptor. These clinical results, associated with the in vitro mitogenic and proteolytic activities of this protein, strongly suggest that the 52-kDa protein staining in tissue is associated with tumor proliferation and/or invasion, rather than with hormone responsiveness.
我们之前描述过一种分子量为52,000的分泌型糖蛋白（52-kDa蛋白），它在某些人乳腺癌细胞系中由雌激素诱导产生。这种蛋白已被鉴定为一种溶酶体组织蛋白酶D样蛋白酶的前体酶，在乳腺癌细胞中大量分泌。为了确定在乳腺肿瘤中检测到该标志物时与激素受体相比可能产生哪些信息，我们使用了与52-kDa蛋白及其相关细胞加工产物（分子量48和34 kDa）特异性相互作用的单克隆抗体。已证实在增殖性导管乳腺病和囊肿中该蛋白浓度较高，这表明其在检测高危乳腺病方面的价值。我们现在展示该蛋白在乳腺癌中的免疫过氧化物酶分布，并与同时检测的胞质激素受体进行比较。在232例乳腺癌中，未发现细胞中52-kDa蛋白含量与胞质雌激素或孕激素受体浓度之间存在相关性。雌激素受体阴性的乳腺癌细胞系对该蛋白的组成性产生也表明了这种缺乏相关性，并且通过对乳腺癌细胞吸出物的双重免疫染色得到证实，显示这种52-kDa溶酶体蛋白酶的细胞质染色与雌激素受体的核染色之间存在分离。这些临床结果，结合该蛋白的体外促有丝分裂和蛋白水解活性，强烈表明组织中52-kDa蛋白染色与肿瘤增殖和/或侵袭相关，而非与激素反应性相关。
