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

研究成果: 雜誌貢獻文章同行評審

129 引文 斯高帕斯(Scopus)


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.
頁(從 - 到)2705-2716
出版狀態已發佈 - 12月 9 1997

ASJC Scopus subject areas

  • 分子生物學
  • 遺傳學
  • 癌症研究


深入研究「ErbB kinases and NDF signaling in human prostate cancer cells」主題。共同形成了獨特的指紋。