Perks C M, Keith A J, Goodhew K L, Savage P B, Winters Z E, Holly J M P
Department of CSSB, Division of Surgery, Level 7, Bristol Royal Infirmary, Bristol BS2 8HW, UK.
Br J Cancer. 2004 Jul 19;91(2):305-11. doi: 10.1038/sj.bjc.6601947.
Human breast cancer is the leading cause of cancer death in women from Western societies, and a large study of the epidemiology demonstrated strong associations between human prolactin and risk of breast cancer. Using established models of apoptosis of human breast cancer cell lines, we assessed the role of prolactin in breast cancer cell growth and survival. We showed that prolactin had no effect on the metabolic activity or total cell number of any cell lines. We confirmed endogenous prolactin production by these cells and that the levels varied. In the presence of a prolactin-neutralising antibody, each of the cell lines responded with the induction of apoptosis as opposed to growth inhibition. The sensitivity of the cell lines to the physiological inducer of apoptosis, C2-ceramide, appeared relative to the levels of endogenous prolactin that they contained. We then showed that exogenously added prolactin acted as a potent survival factor against apoptosis in all the cell lines examined. In addition, we demonstrated that a prolactin-neutralising antibody in combination with C2-ceramide caused an anticipated, additive increase in cell death. This study demonstrated that prolactin protects human breast cancer cell lines against apoptosis and this may have important implications for cancer treatment.
在西方社会,人类乳腺癌是女性癌症死亡的主要原因,一项大型流行病学研究表明,人类催乳素与乳腺癌风险之间存在密切关联。利用已建立的人类乳腺癌细胞系凋亡模型,我们评估了催乳素在乳腺癌细胞生长和存活中的作用。我们发现催乳素对任何细胞系的代谢活性或总细胞数均无影响。我们证实了这些细胞可产生内源性催乳素,且其水平存在差异。在存在催乳素中和抗体的情况下,每个细胞系均表现为诱导凋亡,而非生长抑制。细胞系对凋亡生理诱导剂C2-神经酰胺的敏感性似乎与其所含内源性催乳素水平相关。然后我们发现,外源性添加的催乳素在所有检测的细胞系中均作为一种有效的抗凋亡存活因子发挥作用。此外,我们证明,催乳素中和抗体与C2-神经酰胺联合使用会导致预期的、细胞死亡的累加性增加。这项研究表明,催乳素可保护人类乳腺癌细胞系免受凋亡影响,这可能对癌症治疗具有重要意义。