title: Enhanced caveolin-1 expression increases migration, anchorage-independent growth and invasion of endometrial adenocarcinoma cells.
abstract: BACKGROUND
  Caveolin-1 (CAV1) has been implicated both in tumor suppression and progression, whereby the specific role appears to be context dependent. Endometrial cancer is one of the most common malignancies of the female genital tract; however, little is known about the role of CAV1 in this disease.
  
  
  METHODS
  Here, we first determined by immunohistochemistry CAV1 protein levels in normal proliferative human endometrium and endometrial tumor samples. Then using two endometrial cancer cell lines (ECC: Ishikawa and Hec-1A) we evaluated mRNA and protein levels of CAV1 by real time qPCR and Western blot analysis, respectively. The role of CAV1 expression in ECC malignancy was further studied by either inducing its expression in endometrial cancer cells with the tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate (4β-TPA) or decreasing expression using short-hairpin RNA constructs, and then evaluating the effects of these changes on ECC proliferation, transmigration, matrigel invasion, and colony formation in soft agar.
  
  
  RESULTS
  Immunohistochemical analysis of endometrial epithelia revealed that substantially higher levels of CAV1 were present in endometrial tumors than the normal proliferative epithelium. Also, in Ishikawa and Hec-1A endometrial cancer cells CAV1 expression was readily detectable. Upon treatment with 4β-TPA CAV1 levels increased and coincided with augmented cell transmigration, matrigel invasion, as well as colony formation in soft agar. Reduction of CAV1 expression using short-hairpin RNA constructs ablated these effects in both cell types whether treated or not with 4β-TPA. Alternatively, CAV1 expression appeared not to modulate significantly proliferation of these cells.
  
  
  CONCLUSIONS
  Our study shows that elevated CAV1, observed in patients with endometrial cancer, is linked to enhanced malignancy of endometrial cancer cells, as evidenced by increased migration, invasion and anchorage-independent growth.
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile. nataliadiazvaldivia@gmail.com.|Center for Molecular studies of the Cell (CEMC), Programa de Biologia Celular y Molecular, Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile. nataliadiazvaldivia@gmail.com.
authors.forename: Natalia
authors.initials: N
authors.lastname: Diaz-Valdivia
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile. denbravorod@yahoo.com.|Facultad de Odontología, Universidad de Chile, Santiago, Chile. denbravorod@yahoo.com.
authors.forename: Denisse
authors.initials: D
authors.lastname: Bravo
authors.affiliation: Center for Molecular studies of the Cell (CEMC), Programa de Biologia Celular y Molecular, Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile. hernanhuertac@gmail.com.
authors.forename: Hernán
authors.initials: H
authors.lastname: Huerta
authors.affiliation: Departamento de Obstetricia y Ginecologia, Facultad de Medicina, Hospital Clínico de la Universidad de Chile, Santiago, Chile. soledadhenriquez@yahoo.es.
authors.forename: Soledad
authors.initials: S
authors.lastname: Henriquez
authors.affiliation: Departamento de Obstetricia y Ginecologia, Facultad de Medicina, Hospital Clínico de la Universidad de Chile, Santiago, Chile. gablerf@gmail.com.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gabler
authors.affiliation: Departamento de Obstetricia y Ginecologia, Facultad de Medicina, Hospital Clínico de la Universidad de Chile, Santiago, Chile. mvega@med.uchile.cl.
authors.forename: Margarita
authors.initials: M
authors.lastname: Vega
authors.affiliation: Departamento de Obstetricia y Ginecologia, Facultad de Medicina, Hospital Clínico de la Universidad de Chile, Santiago, Chile. cromero@hcuch.cl.
authors.forename: Carmen
authors.initials: C
authors.lastname: Romero
authors.affiliation: Center for Molecular studies of the Cell (CEMC), Programa de Biologia Celular y Molecular, Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile. ccalderon@med.uchile.cl.
authors.forename: Claudia
authors.initials: C
authors.lastname: Calderon
authors.affiliation: Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. gowen@bio.puc.cl.
authors.forename: Gareth I
authors.initials: GI
authors.lastname: Owen
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile. lleyton@med.uchile.cl.|Center for Molecular studies of the Cell (CEMC), Programa de Biologia Celular y Molecular, Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile. lleyton@med.uchile.cl.
authors.forename: Lisette
authors.initials: L
authors.lastname: Leyton
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile. aquest@med.uchile.cl.|Center for Molecular studies of the Cell (CEMC), Programa de Biologia Celular y Molecular, Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile. aquest@med.uchile.cl.|Laboratorio de Comunicaciones Celulares, Instituto de Ciencias Biomedicas (ICBM). Facultad de Medicina, Universidad de Chile, Av. Indepedencia 1027. Independencia, Santiago, Chile. aquest@med.uchile.cl.
authors.forename: Andrew F G
authors.initials: AF
authors.lastname: Quest
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D051242:Caveolin 1 / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D012333:RNA, Messenger