title: Changes in miR-221/222 Levels in Invasive and In Situ Carcinomas of the Breast: Differences in Association with Estrogen Receptor and TIMP3 Expression Levels.
abstract: Breast cancer (BC) is a heterogeneous group of diseases that still represents a major cause of death in the female population. MicroRNAs (miRNAs, miRs), such as miR-221 and miR-222, have been shown to be involved in BC pathology by acting via its target genes such as tissue inhibitor of metalloproteinase 3 (TIMP3).
  
  
  
  The main goals of this study were to find differences in miR-221/222 levels of expression in BC groups based on invasiveness, and to investigate the association with estrogen receptor (ER), TIMP3 messenger RNA (mRNA) levels, and clinicopathological characteristics of patients and tumors.
  
  
  
  In this study, we measured levels of miR-221/222 in 63 breast tissue samples by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using TaqMan®technology and immunohistochemistry.
  
  
  
  miR-221/222 levels varied significantly across groups based on invasiveness (P < 0.001). In in situ tumors, miR-221 and miR-222 were negatively associated with ER (P = 0.001, r = -0.714, and P = 0.013, r = -0.585, respectively). In invasive breast carcinomas associated with non-invasive tumors, miR-222 was inversely associated with ER (P = 0.039, r = -0.620). Pure invasive BCs showed a positive correlation of miR-221 and miR-222 with TIMP3 mRNA levels (P = 0.008, r = 0.508, and P = 0.010, r = 0.497, respectively).
  
  
  
  An increase in miR-221/222 might be an important event for in situ carcinoma formation, and miR-221/222 may be important molecules that highlight potential differences between invasive breast carcinomas associated with non-invasive and pure invasive BCs.
authors.affiliation: Department for Radiobiology and Molecular Genetics, University of Belgrade-Vinca Institute of Nuclear Sciences, Mike Petrovica Alasa 12-14, 11001, Belgrade, Serbia. dragoninspiration@yahoo.com.
authors.forename: Nina
authors.initials: N
authors.lastname: Petrovic
authors.affiliation: Department for Radiobiology and Molecular Genetics, University of Belgrade-Vinca Institute of Nuclear Sciences, Mike Petrovica Alasa 12-14, 11001, Belgrade, Serbia.
authors.forename: Radoslav
authors.initials: R
authors.lastname: Davidovic
authors.affiliation: Department for Radiobiology and Molecular Genetics, University of Belgrade-Vinca Institute of Nuclear Sciences, Mike Petrovica Alasa 12-14, 11001, Belgrade, Serbia.
authors.forename: Snezana
authors.initials: S
authors.lastname: Jovanovic-Cupic
authors.affiliation: Department for Radiobiology and Molecular Genetics, University of Belgrade-Vinca Institute of Nuclear Sciences, Mike Petrovica Alasa 12-14, 11001, Belgrade, Serbia.
authors.forename: Milena
authors.initials: M
authors.lastname: Krajnovic
authors.affiliation: Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000, Belgrade, Serbia.
authors.forename: Silvana
authors.initials: S
authors.lastname: Lukic
authors.affiliation: Clinic of Maxillofacial Surgery, School of Dental Medicine, University of Belgrade, Dr. Subotica 4, 11000, Belgrade, Serbia.
authors.forename: Milan
authors.initials: M
authors.lastname: Petrovic
authors.affiliation: Department of Pharmacology, School of Dental Medicine, University of Belgrade, Dr. Subotica 8, 11000, Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Roganovic
mesh_terms: D014408:Biomarkers, Tumor; D000071960:Breast Carcinoma In Situ / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; D035683:MicroRNAs; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D019717:Tissue Inhibitor of Metalloproteinase-3; C525709:MIR221, human; C525710:MIR222, human; C088390:TIMP3 protein, human; C508053:ERBB2 protein, human