Declining melatonin levels and MT1 receptor expression in aging rats is associated with enhanced mammary tumor growth and decreased sensitivity to melatonin.
Declining melatonin levels and MT1 receptor expression in aging rats is associated with enhanced mammary tumor growth and decreased sensitivity to melatonin.
复制标题
衰老大鼠中褪黑激素水平和 MT1 受体表达的下降与乳腺肿瘤生长增强和对褪黑激素敏感性降低有关。
DOI：
10.1007/s10549-010-0958-0
复制
发表时间：
2011
影响因子：
3.8
通讯作者：
Blask,DavidE
中科院分区：
文献类型：
--
作者：
Hill,StevenM;Cheng,Chi;Yuan,Lin;Mao,Lulu;Jockers,Ralf;Dauchy,Bob;Frasch,Tripp;Blask,DavidE
据报道，随着乳腺癌发病率的增加，血清褪黑激素（MLT）水平在生命的第5和第6个十年显著降低。考虑到MLT的抗癌活性，我们假设随着女性年龄的增长，与年龄相关的松果体MLT产生的下降导致乳腺癌的发展和生长。在这项研究中，我们试图确定年轻、成年和老年雌性布法罗大鼠中组织分离的乳腺肿瘤的生长是否与MLT及其MT 1受体的年龄相关变化有关。与成年和年轻大鼠相比，老年大鼠的夜间血清MLT峰值水平显著降低。与成年和年轻大鼠相比，在老年大鼠子宫中观察到MT 1-褪黑激素受体的夜间和清晨水平显著降低。与成年或年轻大鼠相比，老年大鼠中移植的、组织分离的、致癌物诱导的乳腺肿瘤的生长率显著增加。与成年和年轻大鼠相比，外源性MLT的生长抑制作用在老年大鼠中减弱。与年轻和成年大鼠相比，老年大鼠肿瘤反应的降低与MT 1受体表达的降低相关。因此，增强的乳腺肿瘤生长与老年和老年期间MLT和MT 1受体水平降低相关，导致对外源性MLT的敏感性降低。最后，我们的研究表明，组织分离的肿瘤模型是可行的模型系统，其中研究的作用，衰老对乳腺癌的生长。
Serum melatonin (MLT) levels have been reported to diminish significantly by the 5th and 6th decades of life as the incidence of breast cancer increases. Given MLT’s anti-cancer activity, we hypothesize that age-related decline in pineal MLT production leads to enhanced breast cancer development and growth as women age. In this study, we sought to determine whether the growth of tissue-isolated mammary tumors in young, adult, and old female Buffalo rats relates to the age-related changes in MLT and its MT1 receptor. Significant decreases in the peak nighttime serum MLT levels were observed in old as compared to adult and young rats. Significantly diminished nighttime and early morning levels of MT1-melatonin receptors were observed in uteri from old rats compared to adult and young rats. Growth rates in transplanted, tissue-isolated, carcinogen-induced mammary tumors are significantly increased in old rats as compared to adult or young rats. The growth-suppressive actions of exogenous MLT are diminished in old rats compared to adult and young rats. This decrease in tumor response correlates with reduced expression of the MT1 receptor in old as compared to young and adult rats. Thus, enhanced mammary tumor growth is associated with old age and diminished levels of MLT and MT1 receptor during old age, resulting in reduced sensitivity to exogenous MLT. Finally, our studies demonstrate that the tissue-isolated tumor model is viable model system in which to study the role of aging on breast cancer growth.