Inhibition of human androgen-independent PC-3 and DU-145 prostate cancers by antagonists of bombesin and growth hormone releasing hormone is linked to PKC, MAPK and c-jun intracellular signalling

Anton Stangelberger, Andrew V Schally, Jozsef L. Varga, Marta Zarandi, Ren Zhi Cai, Benjamin Baker, Brian D. Hammann, Patricia Armatis, Celia A. Kanashiro

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Bombesin/gastrin-releasing peptide (BN/GRP) antagonists RC-3940-II and RC-3940-Et, and growth hormone-releasing hormone (GHRH) antagonists MZ-J-7-118 and RC-J-29-18 inhibit the growth of human androgen-independent PC-3 and DU-145 prostate cancers in nude mice. Additive inhibitory effects were observed after treatment with both classes of analogs. In the present study, we investigated the effects of these antagonists on intracellular signalling pathways of protein kinase C (PKC), mitogen activated protein kinases (MAPK) and c-fos and c-jun oncogenes that are involved in tumour cell proliferation. In PC-3 tumours, antagonists of BN/GRP and GHRH decreased significantly the expression of PKC isoforms alpha (α), eta (η) and zeta (ζ) and increased that of delta (δ) PKC protein. MAPK was not detectable. In DU-145 tumours, which constitutively express MAPK, all treatments strongly decreased the levels of p42/44 MAPK. Treatment with the antagonists tended to reduce m-RNA for c-jun in both tumour models. In proliferation assays in vitro, inhibitors of PKC and MAPK diminished growth of DU-145 and PC-3 cells. These findings suggest that antagonists of BN/GRP and GHRH inhibit the growth of androgen-independent prostate cancer by affecting intracellular signalling mechanisms of PKC, MAPK and c-jun.

Original languageEnglish
Pages (from-to)2735-2744
Number of pages10
JournalEuropean Journal of Cancer
Volume41
Issue number17
DOIs
StatePublished - Nov 1 2005
Externally publishedYes

Fingerprint

Bombesin
Growth Hormone-Releasing Hormone
Mitogen-Activated Protein Kinases
Protein Kinase C
Androgens
Gastrin-Releasing Peptide
Prostatic Neoplasms
Intracellular Signaling Peptides and Proteins
Peptide Hormones
Neoplasms
Growth
jun Genes
Protein Kinase C-delta
Hormone Antagonists
Protein Kinase C-alpha
Mitogen-Activated Protein Kinase 1
Nude Mice
Protein Isoforms
Cell Proliferation
RNA

Keywords

  • c-fos
  • c-jun
  • DU-145
  • MAP-kinases
  • PC-3
  • PKC isoforms
  • Prostate cancer

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Inhibition of human androgen-independent PC-3 and DU-145 prostate cancers by antagonists of bombesin and growth hormone releasing hormone is linked to PKC, MAPK and c-jun intracellular signalling. / Stangelberger, Anton; Schally, Andrew V; Varga, Jozsef L.; Zarandi, Marta; Cai, Ren Zhi; Baker, Benjamin; Hammann, Brian D.; Armatis, Patricia; Kanashiro, Celia A.

In: European Journal of Cancer, Vol. 41, No. 17, 01.11.2005, p. 2735-2744.

Research output: Contribution to journalArticle

Stangelberger, Anton ; Schally, Andrew V ; Varga, Jozsef L. ; Zarandi, Marta ; Cai, Ren Zhi ; Baker, Benjamin ; Hammann, Brian D. ; Armatis, Patricia ; Kanashiro, Celia A. / Inhibition of human androgen-independent PC-3 and DU-145 prostate cancers by antagonists of bombesin and growth hormone releasing hormone is linked to PKC, MAPK and c-jun intracellular signalling. In: European Journal of Cancer. 2005 ; Vol. 41, No. 17. pp. 2735-2744.
@article{fceb76512eea4b68a697b2b04daae7c1,
title = "Inhibition of human androgen-independent PC-3 and DU-145 prostate cancers by antagonists of bombesin and growth hormone releasing hormone is linked to PKC, MAPK and c-jun intracellular signalling",
abstract = "Bombesin/gastrin-releasing peptide (BN/GRP) antagonists RC-3940-II and RC-3940-Et, and growth hormone-releasing hormone (GHRH) antagonists MZ-J-7-118 and RC-J-29-18 inhibit the growth of human androgen-independent PC-3 and DU-145 prostate cancers in nude mice. Additive inhibitory effects were observed after treatment with both classes of analogs. In the present study, we investigated the effects of these antagonists on intracellular signalling pathways of protein kinase C (PKC), mitogen activated protein kinases (MAPK) and c-fos and c-jun oncogenes that are involved in tumour cell proliferation. In PC-3 tumours, antagonists of BN/GRP and GHRH decreased significantly the expression of PKC isoforms alpha (α), eta (η) and zeta (ζ) and increased that of delta (δ) PKC protein. MAPK was not detectable. In DU-145 tumours, which constitutively express MAPK, all treatments strongly decreased the levels of p42/44 MAPK. Treatment with the antagonists tended to reduce m-RNA for c-jun in both tumour models. In proliferation assays in vitro, inhibitors of PKC and MAPK diminished growth of DU-145 and PC-3 cells. These findings suggest that antagonists of BN/GRP and GHRH inhibit the growth of androgen-independent prostate cancer by affecting intracellular signalling mechanisms of PKC, MAPK and c-jun.",
keywords = "c-fos, c-jun, DU-145, MAP-kinases, PC-3, PKC isoforms, Prostate cancer",
author = "Anton Stangelberger and Schally, {Andrew V} and Varga, {Jozsef L.} and Marta Zarandi and Cai, {Ren Zhi} and Benjamin Baker and Hammann, {Brian D.} and Patricia Armatis and Kanashiro, {Celia A.}",
year = "2005",
month = "11",
day = "1",
doi = "10.1016/j.ejca.2005.08.022",
language = "English",
volume = "41",
pages = "2735--2744",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
number = "17",

}

TY - JOUR

T1 - Inhibition of human androgen-independent PC-3 and DU-145 prostate cancers by antagonists of bombesin and growth hormone releasing hormone is linked to PKC, MAPK and c-jun intracellular signalling

AU - Stangelberger, Anton

AU - Schally, Andrew V

AU - Varga, Jozsef L.

AU - Zarandi, Marta

AU - Cai, Ren Zhi

AU - Baker, Benjamin

AU - Hammann, Brian D.

AU - Armatis, Patricia

AU - Kanashiro, Celia A.

PY - 2005/11/1

Y1 - 2005/11/1

N2 - Bombesin/gastrin-releasing peptide (BN/GRP) antagonists RC-3940-II and RC-3940-Et, and growth hormone-releasing hormone (GHRH) antagonists MZ-J-7-118 and RC-J-29-18 inhibit the growth of human androgen-independent PC-3 and DU-145 prostate cancers in nude mice. Additive inhibitory effects were observed after treatment with both classes of analogs. In the present study, we investigated the effects of these antagonists on intracellular signalling pathways of protein kinase C (PKC), mitogen activated protein kinases (MAPK) and c-fos and c-jun oncogenes that are involved in tumour cell proliferation. In PC-3 tumours, antagonists of BN/GRP and GHRH decreased significantly the expression of PKC isoforms alpha (α), eta (η) and zeta (ζ) and increased that of delta (δ) PKC protein. MAPK was not detectable. In DU-145 tumours, which constitutively express MAPK, all treatments strongly decreased the levels of p42/44 MAPK. Treatment with the antagonists tended to reduce m-RNA for c-jun in both tumour models. In proliferation assays in vitro, inhibitors of PKC and MAPK diminished growth of DU-145 and PC-3 cells. These findings suggest that antagonists of BN/GRP and GHRH inhibit the growth of androgen-independent prostate cancer by affecting intracellular signalling mechanisms of PKC, MAPK and c-jun.

AB - Bombesin/gastrin-releasing peptide (BN/GRP) antagonists RC-3940-II and RC-3940-Et, and growth hormone-releasing hormone (GHRH) antagonists MZ-J-7-118 and RC-J-29-18 inhibit the growth of human androgen-independent PC-3 and DU-145 prostate cancers in nude mice. Additive inhibitory effects were observed after treatment with both classes of analogs. In the present study, we investigated the effects of these antagonists on intracellular signalling pathways of protein kinase C (PKC), mitogen activated protein kinases (MAPK) and c-fos and c-jun oncogenes that are involved in tumour cell proliferation. In PC-3 tumours, antagonists of BN/GRP and GHRH decreased significantly the expression of PKC isoforms alpha (α), eta (η) and zeta (ζ) and increased that of delta (δ) PKC protein. MAPK was not detectable. In DU-145 tumours, which constitutively express MAPK, all treatments strongly decreased the levels of p42/44 MAPK. Treatment with the antagonists tended to reduce m-RNA for c-jun in both tumour models. In proliferation assays in vitro, inhibitors of PKC and MAPK diminished growth of DU-145 and PC-3 cells. These findings suggest that antagonists of BN/GRP and GHRH inhibit the growth of androgen-independent prostate cancer by affecting intracellular signalling mechanisms of PKC, MAPK and c-jun.

KW - c-fos

KW - c-jun

KW - DU-145

KW - MAP-kinases

KW - PC-3

KW - PKC isoforms

KW - Prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=27744575622&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27744575622&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2005.08.022

DO - 10.1016/j.ejca.2005.08.022

M3 - Article

C2 - 16291086

AN - SCOPUS:27744575622

VL - 41

SP - 2735

EP - 2744

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

IS - 17

ER -