Skip to main content
NCBI home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1996 Oct;49(10):795–797. doi: 10.1136/jcp.49.10.795

Expression of bcl-2 oncoprotein in pituitary tumours: comparison with c-myc.

D G Wang 1, C F Johnston 1, A B Atkinson 1, A P Heaney 1, M Mirakhur 1, K D Buchanan 1
PMCID: PMC500770  PMID: 8943742

Abstract

AIMS/BACKGROUND: Whereas the control of hormone secretion from pituitary adenomas has been studied in considerable detail, the molecular events underlying the development of these tumours are still poorly understood. Abnormalities of some oncogenes and tumour suppressor genes have been previously reported to occur at very low frequencies. The aim of the present study was to assess the possible expression of the bcl-2 oncoprotein and to compare it with that of c-myc in pituitary adenomas. METHODS: Monoclonal antibodies were used, along with microwave antigen retrieval and the avidin-biotin immunohistochemical method, to investigate expression of the oncoproteins bcl-2 and c-myc in 30 primary pituitary tumours from five broad diagnostic groups and in five normal pituitaries. RESULTS: Bcl-2 and c-myc immunoreactivities were detected in nine (30%) and eight (27%) tumour samples, respectively. Of the nine bcl-2 and eight c-myc positive tumours, seven were positive for both oncoproteins and included one of the four corticotrophinomas studied, four of seven prolactinomas, one of two somatotrophinomas, and one of four oncocytomas. All 13 null cell adenomas studied were negative for both bcl-2 and c-myc immunoreactivities. CONCLUSIONS: These results indicate that the bcl-2 and c-myc oncoproteins are expressed abnormally in over one quarter of pituitary tumours. Most these tumours co-expressed both oncoproteins. The genetic complementation of simultaneously deregulated bcl-2 and c-myc is implicated, through the regulation of apoptosis, in the pathogenesis of pituitary tumours.

Full text

PDF
795

Images in this article

796Image
on p.796

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander J. M., Biller B. M., Bikkal H., Zervas N. T., Arnold A., Klibanski A. Clinically nonfunctioning pituitary tumors are monoclonal in origin. J Clin Invest. 1990 Jul;86(1):336–340. doi: 10.1172/JCI114705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Askew D. S., Ashmun R. A., Simmons B. C., Cleveland J. L. Constitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis. Oncogene. 1991 Oct;6(10):1915–1922. [PubMed] [Google Scholar]
  3. Bishop J. M. The molecular genetics of cancer. Science. 1987 Jan 16;235(4786):305–311. doi: 10.1126/science.3541204. [DOI] [PubMed] [Google Scholar]
  4. Cryns V. L., Alexander J. M., Klibanski A., Arnold A. The retinoblastoma gene in human pituitary tumors. J Clin Endocrinol Metab. 1993 Sep;77(3):644–646. doi: 10.1210/jcem.77.3.7690360. [DOI] [PubMed] [Google Scholar]
  5. Evan G. I., Wyllie A. H., Gilbert C. S., Littlewood T. D., Land H., Brooks M., Waters C. M., Penn L. Z., Hancock D. C. Induction of apoptosis in fibroblasts by c-myc protein. Cell. 1992 Apr 3;69(1):119–128. doi: 10.1016/0092-8674(92)90123-t. [DOI] [PubMed] [Google Scholar]
  6. Fanidi A., Harrington E. A., Evan G. I. Cooperative interaction between c-myc and bcl-2 proto-oncogenes. Nature. 1992 Oct 8;359(6395):554–556. doi: 10.1038/359554a0. [DOI] [PubMed] [Google Scholar]
  7. Herman V., Drazin N. Z., Gonsky R., Melmed S. Molecular screening of pituitary adenomas for gene mutations and rearrangements. J Clin Endocrinol Metab. 1993 Jul;77(1):50–55. doi: 10.1210/jcem.77.1.8100831. [DOI] [PubMed] [Google Scholar]
  8. Herman V., Fagin J., Gonsky R., Kovacs K., Melmed S. Clonal origin of pituitary adenomas. J Clin Endocrinol Metab. 1990 Dec;71(6):1427–1433. doi: 10.1210/jcem-71-6-1427. [DOI] [PubMed] [Google Scholar]
  9. Hockenbery D., Nuñez G., Milliman C., Schreiber R. D., Korsmeyer S. J. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990 Nov 22;348(6299):334–336. doi: 10.1038/348334a0. [DOI] [PubMed] [Google Scholar]
  10. Karga H. J., Alexander J. M., Hedley-Whyte E. T., Klibanski A., Jameson J. L. Ras mutations in human pituitary tumors. J Clin Endocrinol Metab. 1992 Apr;74(4):914–919. doi: 10.1210/jcem.74.4.1312542. [DOI] [PubMed] [Google Scholar]
  11. Korsmeyer S. J. Bcl-2 initiates a new category of oncogenes: regulators of cell death. Blood. 1992 Aug 15;80(4):879–886. [PubMed] [Google Scholar]
  12. Landis C. A., Masters S. B., Spada A., Pace A. M., Bourne H. R., Vallar L. GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours. Nature. 1989 Aug 31;340(6236):692–696. doi: 10.1038/340692a0. [DOI] [PubMed] [Google Scholar]
  13. McDonnell T. J. Cell division versus cell death: a functional model of multistep neoplasia. Mol Carcinog. 1993;8(4):209–213. doi: 10.1002/mc.2940080402. [DOI] [PubMed] [Google Scholar]
  14. McDonnell T. J., Korsmeyer S. J. Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14; 18). Nature. 1991 Jan 17;349(6306):254–256. doi: 10.1038/349254a0. [DOI] [PubMed] [Google Scholar]
  15. Raghavan R., Harrison D., Ince P. G., James R. A., Daniels M., Birch P., Caldwell G. I., Kendall-Taylor P. Oncoprotein immunoreactivity in human pituitary tumours. Clin Endocrinol (Oxf) 1994 Jan;40(1):117–126. doi: 10.1111/j.1365-2265.1994.tb02453.x. [DOI] [PubMed] [Google Scholar]
  16. Schmidt E. V., Pattengale P. K., Weir L., Leder P. Transgenic mice bearing the human c-myc gene activated by an immunoglobulin enhancer: a pre-B-cell lymphoma model. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6047–6051. doi: 10.1073/pnas.85.16.6047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Shi Y., Glynn J. M., Guilbert L. J., Cotter T. G., Bissonnette R. P., Green D. R. Role for c-myc in activation-induced apoptotic cell death in T cell hybridomas. Science. 1992 Jul 10;257(5067):212–214. doi: 10.1126/science.1378649. [DOI] [PubMed] [Google Scholar]
  18. Vallar L., Spada A., Giannattasio G. Altered Gs and adenylate cyclase activity in human GH-secreting pituitary adenomas. Nature. 1987 Dec 10;330(6148):566–568. doi: 10.1038/330566a0. [DOI] [PubMed] [Google Scholar]
  19. Vaux D. L., Cory S., Adams J. M. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature. 1988 Sep 29;335(6189):440–442. doi: 10.1038/335440a0. [DOI] [PubMed] [Google Scholar]
  20. Wagner A. J., Small M. B., Hay N. Myc-mediated apoptosis is blocked by ectopic expression of Bcl-2. Mol Cell Biol. 1993 Apr;13(4):2432–2440. doi: 10.1128/mcb.13.4.2432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wang D. G., Johnston C. F., Anderson N., Sloan J. M., Buchanan K. D. Overexpression of the tumour suppressor gene p53 is not implicated in neuroendocrine tumour carcinogenesis. J Pathol. 1995 Apr;175(4):397–401. doi: 10.1002/path.1711750406. [DOI] [PubMed] [Google Scholar]
  22. Williams G. T., Smith C. A. Molecular regulation of apoptosis: genetic controls on cell death. Cell. 1993 Sep 10;74(5):777–779. doi: 10.1016/0092-8674(93)90457-2. [DOI] [PubMed] [Google Scholar]
  23. Woloschak M., Roberts J. L., Post K. D. Loss of heterozygosity at the retinoblastoma locus in human pituitary tumors. Cancer. 1994 Jul 15;74(2):693–696. doi: 10.1002/1097-0142(19940715)74:2<693::aid-cncr2820740223>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  24. Woloschak M., Roberts J. L., Post K. c-myc, c-fos, and c-myb gene expression in human pituitary adenomas. J Clin Endocrinol Metab. 1994 Jul;79(1):253–257. doi: 10.1210/jcem.79.1.8027238. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES