Abstract

This revised continuation application proposes three specific aims designed to address the role of melatonin in the growth and physiology of human breast cancer: (1) to define the receptor pathway(s), membrane or nuclear, which mediate the growth-inhibitory and ER-modulatory effects of melatonin; (2) to begin to delineate the cellular pathways activated by melatonin and retinoic acid which induce apoptosis in MCF-7 cells; and (3) to move our studies of the apoptotic effects of melatonin and retinoic acid from the in vitro setting to a more physiologically relevant in vivo model system. By defining the role of melatonin in mammary tumorigenesis and its interaction with other hormone pathways, these studies will begin to define the determinants of hormone-responsiveness and hormone-unresponsiveness which are critical in the diagnosis, treatment, and prognosis of breast cancer and may ultimately provide important insight into the prevention of breast cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA054152-09
Application #
6137489
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Jhappan, Chamelli
Project Start
1991-04-01
Project End
2002-04-30
Budget Start
2000-01-05
Budget End
2002-04-30
Support Year
9
Fiscal Year
2000
Total Cost
$178,276
Indirect Cost

  Institution

Name
Tulane University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118

  Publications

Blask, David E; Dauchy, Robert T; Dauchy, Erin M et al. (2014) Light exposure at night disrupts host/cancer circadian regulatory dynamics: impact on the Warburg effect, lipid signaling and tumor growth prevention. PLoS One 9:e102776
Mao, Lulu; Yuan, Lin; Xiang, Shulin et al. (2014) Molecular deficiency (ies) in MT? melatonin signaling pathway underlies the melatonin-unresponsive phenotype in MDA-MB-231 human breast cancer cells. J Pineal Res 56:246-53
Hill, Steven M; Cheng, Chi; Yuan, Lin et al. (2013) Age-related decline in melatonin and its MT1 receptor are associated with decreased sensitivity to melatonin and enhanced mammary tumor growth. Curr Aging Sci 6:125-33
Xiang, Shulin; Mao, Lulu; Yuan, Lin et al. (2012) Impaired mouse mammary gland growth and development is mediated by melatonin and its MT1G protein-coupled receptor via repression of ER?, Akt1, and Stat5. J Pineal Res 53:307-18
Xiang, S; Mao, L; Duplessis, T et al. (2012) Oscillation of clock and clock controlled genes induced by serum shock in human breast epithelial and breast cancer cells: regulation by melatonin. Breast Cancer (Auckl) 6:137-50
Mao, Lulu; Dauchy, Robert T; Blask, David E et al. (2012) Circadian gating of epithelial-to-mesenchymal transition in breast cancer cells via melatonin-regulation of GSK3?. Mol Endocrinol 26:1808-20
Blask, David E; Hill, Steven M; Dauchy, Robert T et al. (2011) Circadian regulation of molecular, dietary, and metabolic signaling mechanisms of human breast cancer growth by the nocturnal melatonin signal and the consequences of its disruption by light at night. J Pineal Res 51:259-69
Hill, Steven M; Cheng, Chi; Yuan, Lin et al. (2011) Declining melatonin levels and MT1 receptor expression in aging rats is associated with enhanced mammary tumor growth and decreased sensitivity to melatonin. Breast Cancer Res Treat 127:91-8
Hill, Steven M; Blask, David E; Xiang, Shulin et al. (2011) Melatonin and associated signaling pathways that control normal breast epithelium and breast cancer. J Mammary Gland Biol Neoplasia 16:235-45
Mao, Lulu; Yuan, Lin; Slakey, Lauren M et al. (2010) Inhibition of breast cancer cell invasion by melatonin is mediated through regulation of the p38 mitogen-activated protein kinase signaling pathway. Breast Cancer Res 12:R107

Showing the most recent 10 out of 18 publications