Bone Microenvironment and Androgen Status Modulate Subcellular Localization of ErbB3 in Prostate Cancer Cells
- 1 July 2007
- journal article
- Published by American Association for Cancer Research (AACR) in Molecular Cancer Research
- Vol. 5 (7), 675-684
- https://doi.org/10.1158/1541-7786.mcr-06-0306
Abstract
ErbB-3, an ErbB receptor tyrosine kinase, has been implicated in the pathogenesis of several malignancies, including prostate cancer. We found that ErbB-3 expression was up-regulated in prostate cancer cells within lymph node and bone metastases. Despite being a plasma membrane protein, ErbB-3 was also detected in the nuclei of the prostate cancer cells in the metastatic specimens. Because most metastatic specimens were from men who had undergone androgen ablation, we examined the primary tumors from patients who have undergone hormone deprivation therapy and found that a significant fraction of these specimens showed nuclear localization of ErbB3. We thus assessed the effect of androgens and the bone microenvironment on the nuclear translocation of ErbB-3 by using xenograft tumor models generated from bone-derived prostate cancer cell lines, MDA PCa 2b, and PC-3. In subcutaneous tumors, ErbB-3 was predominantly in the membrane/cytoplasm; however, it was present in the nuclei of the tumor cells in the femur. Castration of mice bearing subcutaneous MDA PCa 2b tumors induced a transient nuclear translocation of ErbB-3, with relocalization to the membrane/cytoplasm upon tumor recurrence. These findings suggest that the bone microenvironment and androgen status influence the subcellular localization of ErbB-3 in prostate cancer cells. We speculate that nuclear localization of ErbB-3 may aid prostate cancer cell survival during androgen ablation and progression of prostate cancer in bone. (Mol Cancer Res 2007;5(7):675–84)Keywords
This publication has 50 references indexed in Scilit:
- Regulation of Insulin-Like Growth Factor Signaling by Yap Governs Cardiomyocyte Proliferation and Embryonic Heart SizeScience Signaling, 2011
- Expression and Nuclear Localization of ErbB3 in Prostate CancerClinical Cancer Research, 2006
- Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathwayCancer Cell, 2005
- Osteoblasts in prostate cancer metastasis to boneNature Reviews Cancer, 2005
- Dynamic process of prostate cancer metastasis to boneJournal of Cellular Biochemistry, 2003
- Repression of androgen receptor mediated transcription by the ErbB-3 binding protein, Ebp1Oncogene, 2002
- Heregulin-dependent Trafficking and Cleavage of ErbB-4Online Journal of Public Health Informatics, 2000
- Osteomimetic properties of prostate cancer cells: A hypothesis supporting the predilection of prostate cancer metastasis and growth in the bone environmentThe Prostate, 1999
- Prognostic significance of ERRB3 overexpression in oral squamous cell carcinomaCancer Letters, 1995
- Nuclear Localization of P185neu Tyrosine Kinase and Its Association with Transcriptional TransactivationBiochemical and Biophysical Research Communications, 1994