title: The A3 adenosine receptor is highly expressed in tumor versus normal cells: potential target for tumor growth inhibition.
abstract: OBJECTIVE
  A(3) adenosine receptor (A(3)AR) activation was shown to inhibit the growth of various tumor cells via the down-regulation of nuclear factor kappaB and cyclin D1. To additionally elucidate whether A(3)AR is a specific target, a survey of its expression in tumor versus adjacent normal cells was conducted.
  
  
  METHODS
  A(3)AR mRNA expression in various tumor tissues was tested in paraffin-embedded slides using reverse transcription-PCR analysis. A comparison with A(3)AR expression in the relevant adjacent normal tissue or regional lymph node metastasis was performed. In addition, A(3)AR protein expression was studied in fresh tumors and was correlated with that of the adjacent normal tissue.
  
  
  RESULTS
  Reverse transcription-PCR analysis of colon and breast carcinoma tissues showed higher A(3)AR expression in the tumor versus adjacent non-neoplastic tissue or normal tissue. Additional analysis revealed that the lymph node metastasis expressed even more A(3)AR mRNA than the primary tumor tissue. Protein analysis of A(3)AR expression in fresh tumors derived from colon (n = 40) or breast (n = 17) revealed that 61% and 78% had higher A(3)AR expression in the tumor versus normal adjacent tissue, respectively. The high A(3)AR expression level in the tumor tissues was associated with elevated nuclear factor kappaB and cyclin D1 levels. High A(3)AR mRNA expression was also demonstrated in other solid tumor types.
  
  
  CONCLUSIONS
  Primary and metastatic tumor tissues highly express A(3)AR indicating that high receptor expression is a characteristic of solid tumors. These findings and our previous data suggest A(3)AR as a potential target for tumor growth inhibition.
authors.affiliation: Can-Fite BioPharma Ltd., Kiryat-Matalon, Petach-Tikva, Israel.
authors.forename: Lea
authors.initials: L
authors.lastname: Madi
authors.forename: Avivit
authors.initials: A
authors.lastname: Ochaion
authors.forename: Lea
authors.initials: L
authors.lastname: Rath-Wolfson
authors.forename: Sara
authors.initials: S
authors.lastname: Bar-Yehuda
authors.forename: Abigail
authors.initials: A
authors.lastname: Erlanger
authors.forename: Gil
authors.initials: G
authors.lastname: Ohana
authors.forename: Arie
authors.initials: A
authors.lastname: Harish
authors.forename: Ofer
authors.initials: O
authors.lastname: Merimski
authors.forename: Faina
authors.initials: F
authors.lastname: Barer
authors.forename: Pnina
authors.initials: P
authors.lastname: Fishman
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism; D019938:Cyclin D1 / Q000096:biosynthesis; D015536:Down-Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D008207:Lymphatic Metastasis; D008545:Melanoma / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043684:Receptor, Adenosine A3 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D043684:Receptor, Adenosine A3; D019938:Cyclin D1