Alteration of the MT1 melatonin receptor gene and its expression in primary human breast tumors and breast cancer cell lines.
The MT1 melatonin receptor is bound and activated by the pineal hormone melatonin. This G protein-coupled melatonin receptor is expressed in human breast tumor cell lines, and when activated, mediates the growth-suppressive and steroid hormone/nuclear receptor modulatory actions of melatonin on breast tumor cells. In the current studies, we have examined the expression of the MT1 receptor in breast cancer cell lines and primary human breast tumors and correlated MT1 receptor expression with the deletion, rearrangement and amplification of the MT1 gene and established markers of breast cancer such as tumor size, stage, estrogen receptor alpha (ERalpha) and progesterone receptor (PR) expression. Theses studies suggest amplification of the MT1 gene in some breast tumors and an inverse correlation with ERalpha, PR and MT1 protein expression. Furthermore, these approaches employing immunohistochemical and immunofluorescent/confocal microscopic studies demonstrate that the MT1 receptor is localized to the caveoli and that MT1 expression in MCF-7 breast cancer cells can be repressed by estradiol and melatonin.
Lai
Ling
L
Department of Structural & Cellular Biology, Tulane University Health Sciences Center, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Yuan
Lin
L
Cheng
Qi
Q
Dong
Chunmin
C
Mao
Lulu
L
Hill
Steven Marc
SM
D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D021941:Caveolae; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005455:Fluorescent Antibody Technique; D005784:Gene Amplification; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology; D018613:Microscopy, Confocal; D012150:Polymorphism, Restriction Fragment Length; D044122:Receptor, Melatonin, MT1 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D011980:Receptors, Progesterone; D020133:Reverse Transcriptase Polymerase Chain Reaction
D047628:Estrogen Receptor alpha; D004967:Estrogens; D044122:Receptor, Melatonin, MT1; D011980:Receptors, Progesterone; D008550:Melatonin