ErbB kinases and NDF signaling in human prostate cancer cells

Adam W. Grasso, Duanzhi Wen, Casey M. Miller, Johng S. Rhim, Thomas G. Pretlow, Hsing-Jien Kung

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Prostate carcinoma (PCA) is the most commonly diagnosed malignancy in American men. Our knowledge of PCA growth regulation lags behind that of other cancers, such as breast and colon carcinomas. Among receptor tyrosine kinases, the ErbB family is most frequently implicated in neoplasia. We report here the expression of ErbB family kinases and their ligands in PCA cell lines and a xenograft. While ErbB1/EGFR, ErbB2/NEU, and ErbB3 were always observed in a distinct pattern, ErbB4 was not observed. Interestingly, while TGF-α was expressed in the majority of PCA lines, the ligand Neu Differentiation Factor/Heregulin (NDF) was expressed only in an immortalized, non-transformed prostate epithelial line. Concomitantly, there was a significant difference in biological response to these ligands. NDF inhibited LNCaP growth and induced an epithelial-like morphological change, in contrast to TGF-α, which accelerated cell growth. We also performed the first comprehensive analysis of NDF signaling in a prostate line. LNCaP stimulated with NDF demonstrated crosstalk between ErbB3 and ErbB2 which did not involve ErbB1. NDF also turned on several cascades, including those of PI3-K, ERK/MAPK, mHOG/p38 and JNK/SAPK, but not those of PLCγ or the STAT family. This signaling pattern is distinct from that of TGF-α. The activation of mHOG by ErbB2 or ErbB3 has not been reported, and may contribute to the unusual phenotype, PI3-K activation is characterized by the formation of a striking 'activation complex' with multiple tyrosine-phosphorylated species, including ErbB3. Our studies provide a framework in which to dissect the growth and differentiation signals of prostate cancer cells.

Original languageEnglish (US)
Pages (from-to)2705-2716
Number of pages12
JournalOncogene
Volume15
Issue number22
StatePublished - 1997
Externally publishedYes

Fingerprint

Neuregulin-1
Prostatic Neoplasms
Phosphotransferases
Prostate
Carcinoma
Growth
Ligands
Neoplasms
Receptor Protein-Tyrosine Kinases
p38 Mitogen-Activated Protein Kinases
Heterografts
Tyrosine
Colon

Keywords

  • ErbB3
  • Prostate cancer
  • Receptor tyrosine kinase
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Grasso, A. W., Wen, D., Miller, C. M., Rhim, J. S., Pretlow, T. G., & Kung, H-J. (1997). ErbB kinases and NDF signaling in human prostate cancer cells. Oncogene, 15(22), 2705-2716.

ErbB kinases and NDF signaling in human prostate cancer cells. / Grasso, Adam W.; Wen, Duanzhi; Miller, Casey M.; Rhim, Johng S.; Pretlow, Thomas G.; Kung, Hsing-Jien.

In: Oncogene, Vol. 15, No. 22, 1997, p. 2705-2716.

Research output: Contribution to journalArticle

Grasso, AW, Wen, D, Miller, CM, Rhim, JS, Pretlow, TG & Kung, H-J 1997, 'ErbB kinases and NDF signaling in human prostate cancer cells', Oncogene, vol. 15, no. 22, pp. 2705-2716.
Grasso AW, Wen D, Miller CM, Rhim JS, Pretlow TG, Kung H-J. ErbB kinases and NDF signaling in human prostate cancer cells. Oncogene. 1997;15(22):2705-2716.
Grasso, Adam W. ; Wen, Duanzhi ; Miller, Casey M. ; Rhim, Johng S. ; Pretlow, Thomas G. ; Kung, Hsing-Jien. / ErbB kinases and NDF signaling in human prostate cancer cells. In: Oncogene. 1997 ; Vol. 15, No. 22. pp. 2705-2716.
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AB - Prostate carcinoma (PCA) is the most commonly diagnosed malignancy in American men. Our knowledge of PCA growth regulation lags behind that of other cancers, such as breast and colon carcinomas. Among receptor tyrosine kinases, the ErbB family is most frequently implicated in neoplasia. We report here the expression of ErbB family kinases and their ligands in PCA cell lines and a xenograft. While ErbB1/EGFR, ErbB2/NEU, and ErbB3 were always observed in a distinct pattern, ErbB4 was not observed. Interestingly, while TGF-α was expressed in the majority of PCA lines, the ligand Neu Differentiation Factor/Heregulin (NDF) was expressed only in an immortalized, non-transformed prostate epithelial line. Concomitantly, there was a significant difference in biological response to these ligands. NDF inhibited LNCaP growth and induced an epithelial-like morphological change, in contrast to TGF-α, which accelerated cell growth. We also performed the first comprehensive analysis of NDF signaling in a prostate line. LNCaP stimulated with NDF demonstrated crosstalk between ErbB3 and ErbB2 which did not involve ErbB1. NDF also turned on several cascades, including those of PI3-K, ERK/MAPK, mHOG/p38 and JNK/SAPK, but not those of PLCγ or the STAT family. This signaling pattern is distinct from that of TGF-α. The activation of mHOG by ErbB2 or ErbB3 has not been reported, and may contribute to the unusual phenotype, PI3-K activation is characterized by the formation of a striking 'activation complex' with multiple tyrosine-phosphorylated species, including ErbB3. Our studies provide a framework in which to dissect the growth and differentiation signals of prostate cancer cells.

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