Expression of a novel alternatively spliced variant of NADP(H)-dependent retinol dehydrogenase/reductase with deletion of exon 3 in cervical squamous carcinoma
✍ Scribed by Xu-Hong Song; Bin Liang; Ge-Fei Liu; Rui Li; Jian-Ping Xie; Kun Du; Dong-Yang Huang
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- French
- Weight
- 706 KB
- Volume
- 120
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
NADP(H)‐dependent retinol dehydrogenase/reductase (NRDR) plays an important role in maintaining the homeostasis of retinoid. Aberrations in retinoid metabolism are considered as early events in carcinogenesis. We identified a novel alternatively spliced variant, NRDRB~1~, in HeLa cell and human cervical squamous carcinoma tissues, which is characterized by a complete deletion of exon 3. The latter resulted in changes in subcellular localization of NRDRB~1~ when compared with the peroxisomal localization of NRDR. To clarify the clinical significance of NRDRB~1~, we investigated its mRNA and protein expressions in normal cervical and cervical squamous carcinoma tissues, using RT‐PCR, quantitative real‐time PCR, Gateway expressing system, immunoprecipitation, immunoblotting, MALDI‐TOF mass spectrometry and immunohistochemistry. We detected NRDRB~1~ mRNA in 14 of 26 (53.9%) cervical cancer tissues, but in none of the 12 normal cervical tissues. NRDRB~1~ protein was expressed in NRDRB~1~ mRNA‐positive cases. While the full‐length NRDR mRNA was observed in both normal and neoplastic cervical tissues, its protein was only expressed in normal cervical epithelium. The results presented here provide evidence that metabolic disturbances of retinal and retinoic acid, due to abnormal splicing and functional disorder of NRDR, may be involved in cervical tumorigenesis. © 2007 Wiley‐Liss, Inc.