Protein kinase C and growth regulation of pituitary adenomas.
The present study was undertaken to explore the role of the Protein Kinase C (PKC) signal transduction system in growth regulation of pituitary adenomas. Primary tumor cultures were plated from fresh surgical tumor specimens. The PKC inhibitors Staurosporine and Tamoxifen were added at varying dosages to the cell cultures. Measurements of cell proliferation were performed by [3H]-thymidine uptake and the [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide] (MTT) assay. After a 48 h treatment period, both [3H]-thymidine uptake and absorbance on the MTT assay decreased in a dose-related manner in both the staurosporine and tamoxifen-treated cultures (IC50 of 10 nM and 30 microM respectively). Direct measurement of PKC activity using an in vitro assay revealed very high activity (range of 1465-5708 pmol/min/mg protein; within the range previously published for malignant glioma specimens) in 12 frozen specimens of pituitary adenomas (9 nonfunctional adenomas, 1 prolactinoma, 1 gonadotrophin-secreting and 1 corticotroph-secreting adenoma). In contrast, PKC activity measured in normal adenohypophysis was comparatively very low. These data indicate that pituitary adenoma cells display high PKC activity and are sensitive to growth inhibition by PKC inhibitors. These data suggest a role for the PKC system in regulating pituitary tumor growth, which may have implications for future therapy of these tumors.
Couldwell
W T
WT
Department of Neurological Surgery, University of Southern California School of Medicine, Los Angeles, USA.
Law
R E
RE
Hinton
D R
DR
Gopalakrishna
R
R
Yong
V W
VW
Weiss
M H
MH
D000236:Adenoma / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007016:Hypophysectomy; D010902:Pituitary Gland / Q000473:pathology; D010908:Pituitary Hormones, Anterior / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019311:Staurosporine / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology
D010908:Pituitary Hormones, Anterior; D013629:Tamoxifen; D011493:Protein Kinase C; D019311:Staurosporine