title: Gender-related invasion differences associated with mRNA expression levels of melatonin membrane receptors in colorectal cancer.
abstract: Melatonin inhibits growth and invasive capacity of colon cancer cells in vitro through its membrane (MT1 and MT2) and/or nuclear receptors (RORα). Previous studies showed that this indoleamine is present in both the normal and colon cancer at similar levels. Therefore, we analyzed MT1, MT2, and RORα expression in tumor samples versus normal mucosa (NM) from patients suffering from colorectal cancer (CRC). Given the existence of sex differences in the incidence and pathology of CRC and the involvement of steroid receptors in the oncostatic actions of melatonin in some types of cancer, we also analyzed the expression of androgen (AR) and estrogen receptor (ER) α and ERβ. Finally, we conducted some experiments in colon cancer cell lines to corroborate the experiments carried out in human tumors. We found a decreased expression of MT1, MT2, AR, ERα, and ERβ in tumor samples versus NM, but no changes in RORα expression in the whole cohort of patients. Classifying tumors by stage and gender, MT1, MT2, AR, ERα, and ERβ expression decreased in both early stage and advanced tumors, but only in male patients. On the other hand, MT1 and MT2 expression correlated positively with AR, ERα, and ERβ expression in male patients and with ERα or ERβ in female patients. In vitro, the invasive capacity was higher in cells with the least expression of MT1, MT2, and AR, and nonselective MT1/MT2 agonists inhibited cell growth and invasion. These results could indicate a possible interaction of these pathways.
authors.affiliation: San Cecilio University Hospital, Granada, Spain.
authors.forename: Josefa
authors.initials: J
authors.lastname: León
authors.forename: Jorge
authors.initials: J
authors.lastname: Casado
authors.forename: Angel
authors.initials: A
authors.lastname: Carazo
authors.forename: Laura
authors.initials: L
authors.lastname: Sanjuán
authors.forename: Ana
authors.initials: A
authors.lastname: Maté
authors.forename: Paloma
authors.initials: P
authors.lastname: Muñoz de Rueda
authors.forename: Paloma
authors.initials: P
authors.lastname: de la Cueva
authors.forename: Rosa
authors.initials: R
authors.lastname: Quiles
authors.forename: Sergio
authors.initials: S
authors.lastname: Ruíz
authors.forename: Angela
authors.initials: A
authors.lastname: Ruíz-Extremera
authors.forename: Javier
authors.initials: J
authors.lastname: Salmerón
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D015151:Immunoblotting; D007192:Indenes / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives / Q000494:pharmacology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044122:Receptor, Melatonin, MT1 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007192:Indenes; D012333:RNA, Messenger; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D011944:Receptors, Androgen; C024100:6-chloromelatonin; C495910:ramelteon; D008550:Melatonin