PMID- 10318905
OWN - NLM
STAT- MEDLINE
DCOM- 19990617
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 10
DP  - 1999 May 11
TI  - From HER2/Neu signal cascade to androgen receptor and its coactivators: a novel
      pathway by induction of androgen target genes through MAP kinase in prostate
      cancer cells.
PG  - 5458-63
AB  - Overexpression of the HER2/Neu protooncogene has been linked to the progression
      of breast cancer. Here we demonstrate that the growth of prostate cancer LNCaP
      cells can also be increased by the stable transfection of HER2/Neu. Using AG879, 
      a HER2/Neu inhibitor, and PD98059, a MAP kinase inhibitor, as well as MAP kinase 
      phosphatase-1 (MPK-1), in the transfection assay, we found that HER2/Neu could
      induce prostate-specific antigen (PSA), a marker for the progression of prostate 
      cancer, through the MAP kinase pathway at a low androgen level. Reporter assays
      and mammalian two-hybrid assays further suggest this HER2/Neu-induced androgen
      receptor (AR) transactivation may function through the promotion of interaction
      between AR and AR coactivators, such as ARA70. Furthermore, we found this
      HER2/Neu --> MAP kinase --> AR-ARAs --> PSA pathway could not be blocked
      completely by hydroxyflutamide, an antiandrogen used in the treatment of prostate
      cancer. Together, these data provide a novel pathway from HER2/Neu to AR
      transactivation, and they may represent one of the reasons for the PSA
      re-elevation and hormone resistance during androgen ablation therapy in prostate 
      cancer patients.
FAU - Yeh, S
AU  - Yeh S
AD  - George Whipple Laboratory for Cancer Research, Departments of Pathology, Urology,
      Radiation Oncology, and The Cancer Center, University of Rochester, Rochester, NY
      14642, USA.
FAU - Lin, H K
AU  - Lin HK
FAU - Kang, H Y
AU  - Kang HY
FAU - Thin, T H
AU  - Thin TH
FAU - Lin, M F
AU  - Lin MF
FAU - Chang, C
AU  - Chang C
LA  - eng
GR  - F32 CA075732/CA/NCI NIH HHS/United States
GR  - CA55639/CA/NCI NIH HHS/United States
GR  - CA68568/CA/NCI NIH HHS/United States
GR  - CA75732/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (AG-879)
RN  - 0 (Androgen Antagonists)
RN  - 0 (Androgens)
RN  - 0 (Flavonoids)
RN  - 0 (NCOA4 protein, human)
RN  - 0 (Nuclear Receptor Coactivators)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Receptors, Androgen)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Tyrphostins)
RN  - 31D90UKP5Y (hydroxyflutamide)
RN  - 76W6J0943E (Flutamide)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Androgen Antagonists/pharmacology
MH  - Androgens/*genetics/pharmacology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*genetics
MH  - Cell Division/genetics
MH  - Flavonoids/pharmacology
MH  - Flutamide/analogs & derivatives/pharmacology
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Humans
MH  - Male
MH  - Mutagenesis, Site-Directed
MH  - Nuclear Receptor Coactivators
MH  - *Oncogene Proteins
MH  - Prostate-Specific Antigen/genetics
MH  - Prostatic Neoplasms/genetics
MH  - Receptor, ErbB-2/*genetics
MH  - Receptors, Androgen/*genetics
MH  - Signal Transduction
MH  - Trans-Activators/genetics
MH  - *Transcription Factors
MH  - Transcriptional Activation
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Tyrphostins/pharmacology
PMC - PMC21881
EDAT- 1999/05/13 00:00
MHDA- 1999/05/13 00:01
CRDT- 1999/05/13 00:00
PHST- 1999/05/13 00:00 [pubmed]
PHST- 1999/05/13 00:01 [medline]
PHST- 1999/05/13 00:00 [entrez]
AID - 10.1073/pnas.96.10.5458 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 May 11;96(10):5458-63. doi:
      10.1073/pnas.96.10.5458.