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. 1999 Feb;79(5-6):933–939. doi: 10.1038/sj.bjc.6690149

Increased expression of the RIα subunit of the cAMP-dependent protein kinase A is associated with advanced stage ovarian cancer

H M McDaid 1, M T Cairns 1, R J Atkinson 1, S McAleer 1, D P Harkin 1, P Gilmore 1, P G Johnston 1
PMCID: PMC2362667  PMID: 10070893

Abstract

The primary element in the cAMP signal transduction pathway is the cAMP-dependent protein kinase (PKA). Expression of the RIα subunit of type I PKA is elevated in a variety of human tumours and cancer cell lines. The purpose of this study was to assess the prognostic importance of RIα expression in patients with ovarian cancer. We have evaluated the expression of RIα in a panel of human ovarian tumours (n= 40) and five human ovarian cancer cell lines using quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The human ovarian cell lines OAW42 and OTN14 express high endogenous levels of RIα mRNA and protein (at significantly higher mRNA levels than high tissue expressors, P< 0.05). The ovarian cell line A2780 expresses low endogenous levels of RIα mRNA and protein (also at higher mRNA levels than low tissue expressors, P< 0.05). Quantitative RT-PCR revealed no significant difference in RIα mRNA expression between different ovarian histological subtypes in this study. No associations were found between RIα mRNA expression and differentiation state. RIα mRNA expression was significantly associated with tumour stage (P= 0.0036), and this remained significant in univariate analysis (P= 0.0002). A trend emerged between RIα mRNA expression levels and overall survival in univariate analysis (P= 0.051), however, by multivariate analysis, stage remained the major determinant of overall survival (P= 0.0001). This study indicates that in ovarian epithelial tumours high RIα mRNA expression is associated with advanced stage disease. RIα expression may be of predictive value in ovarian cancer and may be associated with dysfunctional signalling pathways in this cancer type. 1999 Cancer Research Campaign

Keywords: type I-cAMP-dependent protein kinase, reverse transcription polymerase chain reaction, ovarian cancer, cAMP

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Selected References

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  1. Beebe S. J. The cAMP-dependent protein kinases and cAMP signal transduction. Semin Cancer Biol. 1994 Aug;5(4):285–294. [PubMed] [Google Scholar]
  2. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  3. Cho-Chung Y. S. Role of cyclic AMP receptor proteins in growth, differentiation, and suppression of malignancy: new approaches to therapy. Cancer Res. 1990 Nov 15;50(22):7093–7100. [PubMed] [Google Scholar]
  4. Langdon S. P., Lawrie S. S., Hay F. G., Hawkes M. M., McDonald A., Hayward I. P., Schol D. J., Hilgers J., Leonard R. C., Smyth J. F. Characterization and properties of nine human ovarian adenocarcinoma cell lines. Cancer Res. 1988 Nov 1;48(21):6166–6172. [PubMed] [Google Scholar]
  5. Leonard M. W., Lim K. C., Engel J. D. Expression of the chicken GATA factor family during early erythroid development and differentiation. Development. 1993 Oct;119(2):519–531. doi: 10.1242/dev.119.2.519. [DOI] [PubMed] [Google Scholar]
  6. Parker S. L., Tong T., Bolden S., Wingo P. A. Cancer statistics, 1996. CA Cancer J Clin. 1996 Jan-Feb;46(1):5–27. doi: 10.3322/canjclin.46.1.5. [DOI] [PubMed] [Google Scholar]
  7. Reimann E. M., Walsh D. A., Krebs E. G. Purification and properties of rabbit skeletal muscle adenosine 3',5'-monophosphate-dependent protein kinases. J Biol Chem. 1971 Apr 10;246(7):1986–1995. [PubMed] [Google Scholar]
  8. Simpson B. J., Ramage A. D., Hulme M. J., Burns D. J., Katsaros D., Langdon S. P., Miller W. R. Cyclic adenosine 3',5'-monophosphate-binding proteins in human ovarian cancer: correlations with clinicopathological features. Clin Cancer Res. 1996 Jan;2(1):201–206. [PubMed] [Google Scholar]
  9. Walsh D. A., Perkins J. P., Krebs E. G. An adenosine 3',5'-monophosphate-dependant protein kinase from rabbit skeletal muscle. J Biol Chem. 1968 Jul 10;243(13):3763–3765. [PubMed] [Google Scholar]
  10. Whelan S. L., Ferlay J. Cancer Incidence in Five Continents. Age-specific and standardized incidence rates. IARC Sci Publ. 1992;(120):178–861. [PubMed] [Google Scholar]
  11. Wilson A. P. Characterization of a cell line derived from the ascites of a patient with papillary serous cystadenocarcinoma of the ovary. J Natl Cancer Inst. 1984 Mar;72(3):513–521. [PubMed] [Google Scholar]
  12. van Niekerk C. C., Poels L. G., Jap P. H., Smeets D. F., Thomas C. M., Ramaekers F. C., Vooijs G. P. Characterization of a human ovarian carcinoma cell line, OTN 14, derived from a mucinous cystadenocarcinoma. Int J Cancer. 1988 Jul 15;42(1):104–111. doi: 10.1002/ijc.2910420120. [DOI] [PubMed] [Google Scholar]

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