Skip to main content
SpringerLink
Log in

Protein Kinase C and Growth Regulation of Pituitary Adenomas

  • Conference paper
Modern Neurosurgery of Meningiomas and Pituitary Adenomas

Part of the book series: Acta Neurochirurgica ((NEUROCHIRURGICA,volume 65))

  • 95 Accesses

Summary

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)-2,5diphenyl-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 µM 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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

Abbreviations

FCS:

fetal calf serum

PMA:

phorbol-12-myristate-13-acetate (phorbol ester; PKC activator)

PKC:

protein kinase C

SP:

staurosporine (PKC inhibitor)

TAM:

tamoxifen (PKC inhibitor)

References

  1. Alvaro V, Touraine Ph, Vozari RR, Bai-Grenier F, Birman P, Joubert D (1992) Protein kinase C activity and expression in normal and adenomatous human pituitaries. Int J Cancer 50: 724–730

    Article  PubMed  CAS  Google Scholar 

  2. Castagna M, Takai Y, Kaibuchi K, Sano K, Kikkawa U, Nishizuka Y (1982) Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem 257: 7847–7851

    PubMed  CAS  Google Scholar 

  3. Couldwell WT, Antel JP, Apuzzo MEJ, Yong VW (1990) Inhibition of growth of established human glioma lines by modulators of the protein kinase C second messenger system. J Neurosurg 73: 594–600

    Article  PubMed  CAS  Google Scholar 

  4. Couldwell WT, Uhm J, Antel JP, Yong VW (1991) Enhanced protein kinase C activity correlates with the growth rate of malignant human gliomas. Neurosurgery 29: 880–887

    Article  PubMed  CAS  Google Scholar 

  5. Couldwell WT, Antel JP, Yong VW (1992) Enhanced protein kinase C activity correlates with the growth rate of malignant gliomas: Part II. Effects of glioma mitogens and modulators of PKC. Neurosurgery 31: 717 724

    Google Scholar 

  6. Dekker LV, Parker PJ (1994) Protein kinase C— a question of specificity. TIBS 19: 73–77

    PubMed  CAS  Google Scholar 

  7. Drust DS, Martin TFJ (1985) Protein kinase C translocates from cytosol to membrane upon hormone activation: Effects of thyrotropin-releasing hormone in GH3 cells. Biochem Biophys Res Commun 128: 531–537

    Article  PubMed  CAS  Google Scholar 

  8. Emoto N, Ohmura E, Isozaki O, Tsuchima T, Shizume K, Demura H (1991) Phorbol ester, not growth hormone releasing factor, consistently stimulates growth hormone release from somatotroph adenomas in culture. Clin Endocrin 34: 377–382

    Article  CAS  Google Scholar 

  9. Fearon CW, Tashjian AH Jr (1985) Thyrotropin-releasing hormone induces redistribution of protein kinase C in GH4C1 rat pituitary cells. J Biol Chem 260: 8366–8371

    PubMed  CAS  Google Scholar 

  10. Fearon CW, Tashjian AH Jr (1987) Ionomycin inhibits thyrotropin-releasing hormone-induced translocation of protein kinase C in GH4C1 pituitary cells. J Biol Chem 262: 9515–9520

    PubMed  CAS  Google Scholar 

  11. Gordeladze JO, Bjoro T, Ostberg BC, Sand O, Torjesen P, Haug E, Gautvik KM (1988) Phorbol esters and thyroliberin have distinct actions regarding stimulation of prolactin secretion and activation of adenylate cyclase in rat anterior pituitary tumor cells (GH4C1). Biochem Pharmacol 37: 3133–3138

    Article  PubMed  CAS  Google Scholar 

  12. Hirota K, Hirota T, Anguilera G, Catt KJ (1985) Hormone-induced redistribution of calcium-activated phospholipiddependent protein kinase in pituitary gonadotrophs. J Biol Chem 260: 3243–3246

    PubMed  CAS  Google Scholar 

  13. Housey GM, Houhnson MD, Hsiao WLW, O’Brian CA, Murphy JP, Kirschmeier P, Weinstein IB (1988) Overproduction of protein kinase C causes disordered growth control in rat fibroblasts. Cell 52: 343–354

    Article  PubMed  CAS  Google Scholar 

  14. Ikuyama S, Nawata H, Kato KI, Natori S, Ibayashi H (1987) Phorbol ester and phospholipase C-induced growth hormone secretion from pituitary somatotroph adenoma cells in culture: effects of somatostatin, bromocriptine, and pertussis toxin. J Clin Endocrin Met 64: 572–577

    Article  CAS  Google Scholar 

  15. Ishizuka T, Ito Y, Murayama M, Miura K, Nagao S, Nozawa Y (1987) Hormone-induced redistribution of protein kinase C in human pituitary adenomas. Clin Chim Acta 170: 351–354

    Article  PubMed  CAS  Google Scholar 

  16. Jin L. Maeda T, Chandler WF, Lloyd RV (1993) Protein kinase C ( PKC) activity and PKC messenger RNAs in human pituitary adenomas. Am J Pathol 142: 569–578

    Google Scholar 

  17. Judd AM, Koike K, Yasumoto T, MacLeod RM (1986) Protein kinase C activators and calcium-mobilizing agents synergistically increase GH, LH, and TSH secretion from anterior pituitary cells. Neuroendocrinology 42: 197

    Google Scholar 

  18. Negro-Vilar A, Lapetina EG (1985) 1,2-Didecanoylglycerol and phorbol 12, 13-dibutyrate enhance anterior pituitary hormone secretion in vitro. Endocrinology 117: 1559

    Google Scholar 

  19. Nishizuka Y (1986) Studies and perspectives on protein kinase C. Science 223: 305–312

    Article  Google Scholar 

  20. Nishizuka Y (1988) The molecular heterogeneity of protein kinase C and its implications for cellular recognition. Nature 334: 661–665

    Article  PubMed  CAS  Google Scholar 

  21. O’Brian CA, Ward NE (1989) Biology of the protein kinase C family. Cancer Metastasis Rev 8: 199–214

    Article  PubMed  Google Scholar 

  22. Ohmura E, Friesen HG (1985) 12-O-Tetradecanoyl phorbol-13acetate stimulates rat growth hormone ( GH) release through different pathways from that of human pancreatic GH-releasingfactors. Endocrinology 116: 728

    Google Scholar 

  23. Persons DA, Wilkison WO, Bell RM, Finn OJ (1988) Altered growth regulation and enhanced tumorigenicity of NIH 3T3 fibroblasts transfected with protein kinase C-1 cDNA. Cell 52: 447–458

    Article  PubMed  CAS  Google Scholar 

  24. Tamaoki T, Nomoto H, Takahashi I, Kato Y, Morimoto M, Tomita F (1986) Staurosporine, a potent inhibitor of phospholipid/Ca++ dependent protein kinase. Biochem Biophys Res Commun 135: 397–402

    Article  PubMed  CAS  Google Scholar 

  25. Todo T, Buchfelder M, Thierauf P, Fahlbusch R (1993) Immunohistochemical expression of protein kinase C type III in human pituitary adenomas. Neurosurgery 32: 635–642

    Article  PubMed  CAS  Google Scholar 

  26. Todo T, Shitara N, Nakamura H, Takakura K, Ikeda K (1991) Immunohistochemical demonstration of protein kinase C isozymes in human brain tumors. Neurosurgery 29: 399–404

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurological Surgery, University of Southern California School of Medicine, Los Angeles, CA, USA

    William T. Couldwell M.D., Ph.D., R. E. Law, D. R. Hinton & M. H. Weiss

  2. Department of Medicine, University of Southern California School of Medicine, Los Angeles, CA, USA

    R. E. Law

  3. Department of Pathology, University of Southern California School of Medicine, Los Angeles, CA, USA

    D. R. Hinton

  4. Department of Cell and Neurobiology, University of Southern California School of Medicine, Los Angeles, CA, USA

    R. Gopalakrishna

  5. Department of Neurology and Neurosurgery, McGill University, Montreal, Canada

    V. W. Yong

Authors
  1. William T. Couldwell M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. E. Law
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. R. Hinton
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Gopalakrishna
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. V. W. Yong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. H. Weiss
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Neurochirurgische Klinik, Universität Erlangen-Nürnberg, Federal Republic of Germany

    Rudolf Fahlbusch , Michael Buchfelder  & Margareta Klinger ,  & 

  2. Neurochirurgische Universitätsklinik, Düsseldorf, Federal Republic of Germany

    Wolfgang J. Bock

  3. Neurochirurgische Universitätsklinik, Berlin, Federal Republic of Germany

    Mario Brock

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer-Verlag

About this paper

Cite this paper

Couldwell, W.T., Law, R.E., Hinton, D.R., Gopalakrishna, R., Yong, V.W., Weiss, M.H. (1996). Protein Kinase C and Growth Regulation of Pituitary Adenomas. In: Fahlbusch, R., Bock, W.J., Brock, M., Buchfelder, M., Klinger, M. (eds) Modern Neurosurgery of Meningiomas and Pituitary Adenomas. Acta Neurochirurgica, vol 65. Springer, Vienna. https://doi.org/10.1007/978-3-7091-9450-8_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-9450-8_8

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-9452-2

  • Online ISBN: 978-3-7091-9450-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation