Increased retinoic acid receptor-beta4 correlates in vivo with reduced retinoic acid receptor-beta2 in esophageal squamous cell carcinoma.

Abstract

Different retinoic acid receptor-beta (RAR-beta) isoforms seem to have contrasting biological effects in human carcinogenesis. Both in vitro and in vivo data indicate that RAR-beta2 expression is frequently lost or reduced (and transfecting RAR-beta2 suppresses growth and promotes apoptosis) in various cancer cells and tissues, whereas RAR-beta4 expression is increased in several cancer cell lines. To clarify the effects of different RAR-beta isoforms in esophageal carcinogenesis, we used real-time quantitative reverse transcription-PCR to assess in vivo RAR-beta mRNA levels in specimens of normal and malignant human esophageal tissue, comparing these levels with each other and the expressions of other genes. RAR-beta2 mRNA expression was significantly reduced (i.e., lower in cancer than normal tissue) in 67% (18 of 27, P = 0.001) and RAR-beta(4) mRNA was increased in 52% (14 of 27, P = 0.054) of our esophageal cancer cases. The expressions of RAR-beta1, chicken ovalbumin upstream promoter-transcription factor-I (COUP-TFI), COUP-TFII, and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) mRNA were reduced, whereas epidermal growth factor receptor and cyclin D1 expressions were increased in tumor compared with in normal tissues. Reduced RAR-beta2 expression correlated with increased RAR-beta4 expression (P = 0.002) and with the suppression of COUP-TFI and COUP-TFII (P = 0.050 and 0.023, respectively) in tumor samples. These are the first in vivo expression patterns of RAR-beta2 and RAR-beta4 reported in humans or animals and support the in vitro data on these isoforms and their contrasting biological effects in human carcinogenesis.

• Authors: Xiao-chun Xu, J Jack Lee, Tsung-Teh Wu, Ashraful Hoque, Jeffer A Ajani, Scott M Lippman
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 14 Issue 4 Pg. 826-9 (Apr 2005) ISSN: 1055-9965 [Print] United States
• PMID: 15824151 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Protein Isoforms
• Receptors, Retinoic Acid

Topics

• Carcinoma, Squamous Cell (genetics)
• Esophageal Neoplasms (genetics)
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Protein Isoforms (genetics)
• Receptors, Retinoic Acid (genetics)
• Reverse Transcriptase Polymerase Chain Reaction