title: Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.
abstract: Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression.
authors: Molecular Chemoprevention Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors: Claudio
authors: C
authors: Pulito
authors: Department of Epidemiology, Regina Elena National Cancer Institute, Rome, Italy.
authors: Irene
authors: I
authors: Terrenato
authors: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors: Anna
authors: A
authors: Di Benedetto
authors: Molecular Chemoprevention Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors: Etleva
authors: E
authors: Korita
authors: Translational Oncogenomics Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors: Frauke
authors: F
authors: Goeman
authors: Translational Oncogenomics Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors: Andrea
authors: A
authors: Sacconi
authors: Translational Oncogenomics Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors: Francesca
authors: F
authors: Biagioni
authors: Translational Oncogenomics Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors: Giovanni
authors: G
authors: Blandino
authors: Molecular Chemoprevention Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors: Sabrina
authors: S
authors: Strano
authors: Department of Oncology, Juravinski Cancer Center-McMaster University Hamilton, Hamilton, ON L8V 5C2, Ontario, Canada.
authors: Paola
authors: P
authors: Muti
authors: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors: Marcella
authors: M
authors: Mottolese
authors: Laboratory of Pharmacogenomics (Area Molecular Medicine), Regina Elena National Cancer Institute, Rome, Italy.
authors: Elisabetta
authors: E
authors: Falvo
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000071616:CDX2 Transcription Factor; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*; D012189:Retrospective Studies; D014807:Vitamin D / Q000494:pharmacology
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014807:Vitamin D