Endothelin-3 growth factor levels decreased in cervical cancer compared with normal cervical epithelial cells.
We used cDNA microarray analysis of RNA extracted from normal, dysplastic, and cancerous cervical tissues to identify the changes in gene expression during the procession from normal to cancerous cervical epithelial cells. We found the expression of 5 genes in cancerous cervical epithelial cells that were not found in normal cervical epithelial cells, among which were lymphoid-restricted membrane protein, protease serine 2, WD repeat domain 59, thyrotropin-releasing hormone degrading enzyme, and the endothelin-3 growth factor. We then analyzed the expression levels of endothelin growth factors 1, 2, and 3 (ET-1, ET-2, and ET-3) and their receptors A and B (ETR-A and ETR-B) by reverse transcriptase-polymerase chain reaction in 3 cervical cancer cell lines and by immunohistochemical staining in cervical normal, dysplastic, and cancer tissues. ET-1, ET-2, and ET-3 growth factor levels were detectable in the maturing layer of cervical epithelium but not in the germinal layer. All 3 growth factors (ET-1, ET-2, and ET-3) were detected in the cytoplasm of the maturing normal cervical epithelial cells. In addition, there were decreased levels of ET-3 and increased levels of ET-1, ET-2, ETR-A, and ETR-B in cancerous cervical epithelial cells compared with normal cervical epithelial cells. These results suggest that the reduction of ET-3 growth factor levels may be important in the transition from normal to cancerous cervical epithelium.
Sun
De Jun
J
Gene Therapy Program, Sidney Kimmel Cancer Center, San Diego, CA 92121, USA.
Liu
Ying
Y
Gene Therapy Program, Sidney Kimmel Cancer Center, San Diego, CA 92121, USA.
Lu
Dong Cheng
DC
Medical Oncology Section, Department of Medicine, Yale University School of Medicine, New Haven, CT 06250, USA.
Kim
Woonbong
W
Gene Therapy Program, Sidney Kimmel Cancer Center, San Diego, CA 92121, USA.
Lee
Je Ho
JH
Molecular Therapy Research, School of Medicine, Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea.
Maynard
Jonathan
J
Gene Therapy Program, Sidney Kimmel Cancer Center, San Diego, CA 92121, USA.
Deisseroth
Albert
A
Gene Therapy Program, Sidney Kimmel Cancer Center, San Diego, CA 92121, USA. Electronic address: adeisseroth@skcc.org.
D045744:Cell Line, Tumor; D002584:Cervix Uteri / Q000378:metabolism*; D019332:Endothelin-1 / Q000378:metabolism; D019333:Endothelin-2 / Q000378:metabolism; D019334:Endothelin-3 / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
D019332:Endothelin-1; D019333:Endothelin-2; D019334:Endothelin-3; D016232:Endothelins; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B