Biological Functions of LSAMP, a Gene Associated with Rapid Disease Progression in Prostate Cancer
Abstract
African American men have the highest prostate cancer incidence and mortality rates in the US. However, the biological basis for this disparity is not well understood. LSAMP inactivation has been implicated in various cancers, and recently identified in prostate cancer. A higher frequency of genomic inactivation was observed in AA prostate cancer, and this aberration significantly associated with rapid disease progression. However, the putative tumor suppressive function of LSAMP has not been characterized. METHODS: The copy number and expression of LSAMP in prostate cancer cell lines was assessed. LNCaP, MDA PCa 2b, and DU 145 cell lines were stably transduced to express LSAMP in an inducible or constitutive manner. Proliferation and tumor growth rates were assessed by MTT assay, and subcutaneous xenograft model. LSAMP expressing and control DU 145 cells were used to assess extracellular matrix-cell adhesion, and cell-cell adhesion to fibroblast (NIH/3T3), normal human prostate stroma derived (WPMY-1), and human endothelial (HUVEC) cell monolayers. LSAMP inhibition of specific signal transduction in prostate cancer cell lines was assessed by immunoblot and immunofluorescence assays. RESULTS: Expression of LSAMP inhibited cell proliferation and tumor growth, and increased adhesion to extracellular matrix proteins. LSAMP expression also increased cell-adhesion to fibroblast and prostate stroma cell lines, and concomitantly decreased endothelial cell-adhesion. Furthermore, LSAMP decreased expression of specific receptor tyrosine kinases: FGFR2, FGFR4, and EPHA3, resulting in decreased phosphorylation of their downstream targets in the Akt and ERK1/2 signaling pathways, and leading to the dysregulation of -catenin. Additionally, LSAMP alters the expression of several Integrins.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 16, 2018
- Accession Number
- AD1128051
Entities
People
- Kevin Babcock
Organizations
- Uniformed Services University of the Health Sciences