Increased retinoic acid receptor-beta4 correlates in vivo with reduced retinoic acid receptor-beta2 in esophageal squamous cell carcinoma.
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.
Xu
Xiao-chun
XC
Department of Clinical Cancer Prevention, Unit 1360, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. xxu@mdanderson.org
Lee
J Jack
JJ
Wu
Tsung-Teh
TT
Hoque
Ashraful
A
Ajani
Jeffer A
JA
Lippman
Scott M
SM
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020033:Protein Isoforms; D018168:Receptors, Retinoic Acid