Differential expression of GRK isoforms in nonmalignant and malignant human granulosa cells.
Granulosa cell tumors are serious ovarian neoplasms that can occur in women of all ages. While there have been numerous attempts to understand the cause of these malignancies, the pathogenesis of granulosa cell tumors (GCTs) still remains largely unknown. G-protein coupled receptor kinases (GRKs) are important regulators of signal transduction through the process of receptor desensitization and internalization. Receptors that are regulated by GRKs are members of the large family of seven-transmembrane receptors and include the follicle stimulating hormone receptor (FSHR). In granulosa cells, the FSH signaling system is responsible for cell proliferation, differentiation, and steroidogenesis. In the studies presented, we examined GRK mRNA and protein expression in nonmalignant human granulosa cells, in KGN cells, a human GCT cell line, and in a panel of human GCT samples. The KGN tumor cells express significantly less GRK4 alpha/beta protein and higher levels of GRK2 and GRK4 gamma/delta protein as compared to nonmalignant human granulosa cells. In human GCT samples, GRK4 alpha/beta protein was detected in 3 of the 13 tumor samples, whereas gamma/delta proteins expression was detected in all samples. These findings suggest that GRK protein expression is altered in GCTs and may be involved in the pathogenesis of these tumors.
King
Denise Walker
DW
Section of Pediatric Endocrinology/Diabetology, Department of Pediatrics, Physiology and Biophysics, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Steinmetz
Rosemary
R
Wagoner
Heather A
HA
Hannon
Tamara S
TS
Chen
Lin Yuan
LY
Eugster
Erica A
EA
Pescovitz
Ora Hirsch
OH
D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006106:Granulosa Cell Tumor / Q000737:chemistry*; D006801:Humans; D010051:Ovarian Neoplasms / Q000737:chemistry*; D020033:Protein Isoforms; D011494:Protein Kinases / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D011962:Receptors, FSH / Q000032:analysis*; D043562:Receptors, G-Protein-Coupled / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020033:Protein Isoforms; D012333:RNA, Messenger; D011962:Receptors, FSH; D043562:Receptors, G-Protein-Coupled; D011494:Protein Kinases