The A3 Adenosine Receptor Is Highly Expressed in Tumor versus Normal Cells

• Published in: Clinical cancer research 2004-07, Vol.10 (13), p.4472-4479
• Main Authors: Madi, Lea, Ochaion, Avivit, Rath-Wolfson, Lea, Bar-Yehuda, Sara, Erlanger, Abigail, Ohana, Gil, Harish, Arie, Merimski, Ofer, Barer, Faina, Fishman, Pnina
• Format: Article
• Language: English
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-03-0651

Purpose: 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 κB 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. Experimental Design: 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 κB 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.