Declining melatonin levels and MT1 receptor expression in aging rats is associated with enhanced mammary tumor growth and decreased sensitivity to melatonin
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Steven M. Hill Chi Cheng Lin Yuan Lulu Mao Ralf Jockers Bob Dauchy Tripp Frasch David E. Blask
- چاپ و سال / کشور: 2010
Description
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 agerelated 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, tissueisolated, 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.
Breast Cancer Res Treat (2011) 127:91–98 DOI 10.1007/s10549-010-0958-0 Received: 20 March 2010 / Accepted: 14 May 2010 / Published online: 12 June 2010 Springer Science+Business Media, LLC. 2010
