Cassoni P, Sapino A, Haagensen D E, Naldoni C, Bussolati G
Department of Biomedical Sciences and Oncology, University of Turin, Italy.
Int J Cancer. 1995 Jan 17;60(2):216-20. doi: 10.1002/ijc.2910600215.
The biological significance of a major protein component in the fluid of gross cystic breast disease and a recognized marker of apocrine metaplasia, i.e. the 15-kDa glycoprotein (GCDFP-15), is presently unknown. We have added GCDFP-15 to cell culture medium and tested its effect on proliferation of 4 human breast-cancer cell lines (MCF7, BT474, MDA-MB231 and T47D) and a "normal" human immortal breast-cell line (MCF10A). These breast-cell lines showed a mitogenic response to GCDFP-15 (10 micrograms/ml). GCDFP-15 enhanced cell growth of the MCF10A, MCF7, BT474 and MDA-MB231 cell lines at both 48 and 96 hr of exposure. The glycoprotein exerted a mitogenic effect on the T47D cell line at 48 hr but not at 96 hr. This may be due to an auto-regulatory effect of endogenous GCDFP-15 synthesized by the T47D cells. GCDFP-15 was ineffective on 2 colon-cancer cell lines (HT29 and NIC-H716), on the IMR32 neuroblastoma cell line and on the NIC-H209 small-cell lung carcinoma cells. A separate major breast cystic disease fluid protein of 24 kDa (GCDFP-24) was tested, following the same experimental design, on the 5 breast-cell lines, and showed no mitogenic activity. The mitogenic effect of GCDFP-15 observed in this study in both "normal" and malignant breast epithelial cells suggests a possible relationship between apocrine metaplasia in breast cystic disease and the development of breast epithelial hyperplasia. In addition, a possible role of GCDFP-15 in breast-cancer progression should be considered.
乳腺大汗腺化生的一个公认标志物、即15-kDa糖蛋白（GCDFP-15），作为乳腺大囊性病囊液中的一种主要蛋白质成分，其生物学意义目前尚不清楚。我们已将GCDFP-15添加到细胞培养基中，并测试了其对4种人乳腺癌细胞系（MCF7、BT474、MDA-MB231和T47D）以及一种“正常”人永生化乳腺细胞系（MCF10A）增殖的影响。这些乳腺细胞系对GCDFP-15（10微克/毫升）呈现出促有丝分裂反应。在暴露48小时和96小时时，GCDFP-15均增强了MCF10A、MCF7、BT474和MDA-MB231细胞系的细胞生长。该糖蛋白在48小时时对T47D细胞系有促有丝分裂作用，但在96小时时则无此作用。这可能是由于T47D细胞合成的内源性GCDFP-15的自身调节作用。GCDFP-15对2种结肠癌细胞系（HT29和NIC-H716）、IMR32神经母细胞瘤细胞系以及NIC-H209小细胞肺癌细胞均无作用。按照相同的实验设计，对5种乳腺细胞系测试了另一种24-kDa的乳腺大囊性病囊液主要蛋白（GCDFP-24），结果显示其无促有丝分裂活性。本研究中在“正常”和恶性乳腺上皮细胞中均观察到的GCDFP-15的促有丝分裂作用提示，乳腺大囊性病中的大汗腺化生与乳腺上皮增生的发生之间可能存在关联。此外，应考虑GCDFP-15在乳腺癌进展中的可能作用。
