Journal of Molecular Histology

, Volume 37, Issue 1–2, pp 37–41 | Cite as

Co-expression of interleukin-6 and human growth hormone in apparently normal prostate biopsies that ultimately progress to prostate cancer using low pH, high temperature antigen retrieval

Original Paper


Prostate cancer is the most common cancer in American men and the second leading cause of cancer deaths in this group. Both growth hormone (GH) and the inflammatory cytokine interleukin 6 (IL-6) have been implicated in prostate cancer progression. Studies in other systems have shown that an increase in GH results in an increase in IL-6 also. The current study demonstrated a parallel spatial and temporal expression of GH and IL-6 in cells in prostate cancer glandular acina cells. This study cannot determine if this expression is coincidental or causative, but it seems likely that the increase in GH could induce the expression of IL-6, since this is the case in other tissues. Optimal labelling for IL-6 in our study was achieved with low pH, high temperature antigen retrieval.


Prostate Cancer Immunolabeling IL-6 GH 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



The authors wish to acknowledge the Rebecca L Cooper Medical Research Foundation which provided a grant for this study.


  1. Akakura K, Suzuki H, Ueda T, Komiya A, Ichikawa T, Igarashi T, Ito H (2003) Possible mechanism of dexamethasone therapy for prostate cancer: suppression of circulating level of interleuin-6. Prostate 56:106–109PubMedCrossRefGoogle Scholar
  2. Chopin LK, Veveris-Lowe TL, Philipps AF, Herington AC (2002) Co-expression of GH and GHR isoforms in prostate cancer cell lines. Growth Horm IGF Res 12:126–136PubMedCrossRefGoogle Scholar
  3. Chung TD, Yu JJ, Spiotto MT, Bartkowski M, Simons JW (1999) Characterization of the role of IL-6 in the progression of prostate cancer. Prostate 38:199–207PubMedCrossRefGoogle Scholar
  4. Culig Z, Bartsch G, Hobisch A (2002) Interleukin-6 regulates androgen receptor activity and prostate cancer cell growth. Mol Cell Endocrinol 197:231–238PubMedCrossRefGoogle Scholar
  5. Fasshauer M, Klein J, Lossner U, Paschke R (2003) Interleukin (IL)-6 mRNA expression is stimulated by insulin, isoproterenol, tumour necrosis factor alpha, growth hormone, and IL-6 in 3T3-L1 adipocytes. Horm Metab Res 35:147–152PubMedCrossRefGoogle Scholar
  6. Giri D, Ozen M, Ittmann M (2001) Interleukin-6 is an autocrine growth factor in human prostate cancer. Am J Pathol 159:2159–2165PubMedGoogle Scholar
  7. Goh EL, Pircher TJ, Wood TJ, Norstedt G, Graichen R, Lobie PE (1997) Growth hormone-induced reorganization of the actin cytoskeleton is not required for STAT5 (signal transducer and activator of transcription-5)-mediated transcription. Endocrinology 138:3207–3215PubMedCrossRefGoogle Scholar
  8. Hobisch A, Rogatsch H, Hittmair A, Fuchs D, Bartsch G Jr, Klocker H, Bartsch G, Culig Z (2000) Immunohistochemical localization of interleukin-6 and its receptor in benign, premalignant and malignant prostate tissue. J Pathol 191:239–244PubMedCrossRefGoogle Scholar
  9. Hull KL, Harvey S (2001) Growth hormone: roles in female reproduction. J Endocrinol 168:1–23PubMedCrossRefGoogle Scholar
  10. Ibanez L, Fucci A, Valls C, Ong K, Dunger D, de Zegher F (2005) Neutrophil count in small-for-gestational age children: contrasting effects of metformin and growth hormone therapy. J Clin Endocrinol Metab 90:3435–3439PubMedCrossRefGoogle Scholar
  11. Kaulsay KK, Mertani HC, Tornell J, Morel G, Lee KO, Lobie PE (1999) Autocrine stimulation of human mammary carcinoma cell proliferation by human growth hormone. Exp Cell Res 250:35–50PubMedCrossRefGoogle Scholar
  12. Khorram O, Garthwaite M, Grosen E, Golos T (2001) Human uterine and ovarian expression of growth hormone-releasing hormone messenger RNA in benign and malignant gynecologic conditions. Fertil Steril 75:174–179PubMedCrossRefGoogle Scholar
  13. Lee SO, Lou W, Hou M, de Miguel F, Gerber L, Gao AC (2003) Interleukin-6 promotes androgen-independent growth in LNCaP human prostate cancer cells. Clin Cancer Res 9:370–376PubMedGoogle Scholar
  14. Milch RA, Rall DP, Tobie JE (1957) Bone Localization of the Tetracyclines. J Natl Cancer Inst 19:87–93PubMedGoogle Scholar
  15. Mukhina S, Mertani H, Guo K, Lee C, PD Gluckman, Lobie P (2004) Phenotypic conversion of human mammary carcinoma cells by autocrine human growth hormone. Proc Natl Acad Sci USA 101:1–6CrossRefGoogle Scholar
  16. Nakashima J, Tachibana M, Horiguchi Y, Oya M, Ohigashi T, Asakura H, Murai M (2000) Serum interleukin 6 as a prognostic factor in patients with prostate cancer. Clin Cancer Res 6:2702–2706PubMedGoogle Scholar
  17. Ogilvy-Stuart AL, Gleeson H (2004) Cancer risk following growth hormone use in childhood: implications for current practice. Drug Saf 27:369–382PubMedCrossRefGoogle Scholar
  18. Pagani S, Meazza C, Travaglino P, De Benedetti F, Tinelli C, Bozzola M (2005) Serum cytokine levels in GH-deficient children during substitutive GH therapy. Eur J Endocrinol 52:207–210PubMedCrossRefGoogle Scholar
  19. Park JI, Lee MG, Cho K, Park BJ, Chae KS, Byun DS, Ryu BK, Park YK, Chi SG (2003) Transforming growth factor-beta1 activates interleukin-6 expression in prostate cancer cells through the synergistic collaboration of the Smad2, p38-NF-kappaB, JNK, and Ras signaling pathways. Oncogene 22:4314–4332PubMedCrossRefGoogle Scholar
  20. Raccurt M, Lobie PE, Moudilou E, Garcia-Caballero T, Frappart L, Morel G, Mertani HC (2002) High stromal and epithelial human gh gene expression is associated with proliferative disorders of the mammary gland. J Endocrinol 175:307–318PubMedCrossRefGoogle Scholar
  21. Royuela M, Ricote M, Parsons MS, Garcia-Tunon I, Paniagua R, de Miguel MP (2004) Immunohistochemical analysis of the IL-6 family of cytokines and their receptors in benign, hyperplasic, and malignant human prostate. J Pathol 202:41–49PubMedCrossRefGoogle Scholar
  22. Schindler AE (2004) Gonadotropin-releasing hormone agonists for prevention of postoperative adhesions: an overview. Gynecol Endocrinol 19:51–55PubMedCrossRefGoogle Scholar
  23. Siejka A, Stepien T, Lawnicka H, Krupinski R, Komorowski J, Stepien H (2005) Effect of the growth hormone-releasing hormone [GHRH(1-44)NH2] on IL-6 and IL-8 secretion from human peripheral blood mononuclear cells in vitro. Endocr Regul 39:7–11PubMedGoogle Scholar
  24. Slater M (1999) Mitochondrial DNA damage assessment using fluorescence microscopy quantitation. J Histotechnol 22:17–21Google Scholar
  25. Slater M, Murphy CR (1999) Detection of apoptotic DNA damage in prostate hyperplasia using tyramide-amplified avidin-HRP. Histochem J 31:747–749PubMedCrossRefGoogle Scholar
  26. Steiner H, Godoy-Tundidor S, Rogatsch H, Berger AP, Fuchs D, Comuzzi B, Bartsch G, Hobisch A, Culig Z (2003) Accelerated in vivo growth of prostate tumors that upregulate interleukin-6 is associated with reduced retinoblastoma protein expression and activation of the mitogen-activated protein kinase pathway. Am J Pathol 162:655–663PubMedGoogle Scholar
  27. Swolin D, Ohlsson C (1996) Growth hormone increases interleukin-6 produced by human osteoblast-like cells. J Clin Endocrinol Metab 81:4329–4333PubMedCrossRefGoogle Scholar
  28. Triantafillidis JK, Merikas E, Govosdis V, Konstandellou E, Cheracakis P, Barbatzas C, Tzourmakliotis D, Peros G (2003) Increased fasting serum levels of growth hormone and gastrin in patients with gastric and large bowel cancer. Hepato-Gastroenterology 50(Suppl 2):cclvi–cclxPubMedGoogle Scholar
  29. Uronen-Hansson H, Allen ML, Lichtarowicz-Krynska E, Aynsley-Green A, Cole TJ, Hoiden-Guthenberg I, Fryklund L, Klein N (2003) Growth hormone enhances proinflammatory cytokine production by monocytes in whole blood. Growth Horm IGF Res 13:282–286PubMedCrossRefGoogle Scholar
  30. Wang P, Li N, Li JS, Li WQ (2002)The role of endotoxin, TNF-alpha, and IL-6 in inducing the state of growth hormone insensitivity. World J Gastroenterol 8:531–536PubMedMATHGoogle Scholar
  31. Yang L, Wang L, Lin HK, Kan PY, Xie S, Tsai MY, Wang PH, Chen YT, Chang C (2003) Interleukin-6 differentially regulates androgen receptor transactivation via PI3K-Akt, STAT3, and MAPK, three distinct signal pathways in prostate cancer cells. Biochem Biophys Res Commun 305:462–469PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  1. 1.School of Medical Sciences, Department of Anatomy and Histology F13The University of SydneySydneyAustralia

Personalised recommendations