Enhanced expression of SOS1 is detected in prostate cancer epithelial cells from African-American men

Int J Oncol. 2009 Oct;35(4):751-60.

Abstract

African-American (AA) men experience an increased risk of developing prostate cancers as well as increased mortality following treatment as compared to European-American (EA) men. The aim of our study was to identify biological factors with the potential to predispose AA men to prostate tumor progression and metastasis. To identify cancer-specific gene expression patterns in AA men, we established primary prostate cancer epithelial cells from 14 AA and 13 EA men. High-throughput microarrays were used to investigate differences in global gene expression comparing the two groups. Quantitative RT-PCR and immunohistochemistry validated mRNA and protein expression levels. RNAi knockdowns provided support for biological significance for the identified genes in prostate cancer cells. Son of sevenless homolog 1 (SOS1) was overexpressed in AA male-derived primary prostate cancer epithelial cells. Depletion of SOS1 in PC3 and DU145 prostate cancer cells resulted in decreased capacities for cell proliferation, migration and invasion, at least partially through inhibition of extracellular signal-regulated kinase 1 and 2. Tissue microarray analyses of SOS1 expression in prostate carcinomas correlated with Gleason's grades of tumors, consistent with a possible role in prostate cancer progression. Investigation of prostate cancer-derived epithelial cells has led to identification of SOS1 as a potential candidate biomarker and molecular therapeutic target in prostate cancer in AA men, consistent with the hypothesis that a biological basis exists for prostate cancer aggressiveness in AA men.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / ethnology*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / secondary
  • Adenocarcinoma / surgery
  • African Continental Ancestry Group* / genetics
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial Cells / metabolism*
  • European Continental Ancestry Group* / genetics
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Prostatectomy
  • Prostatic Neoplasms / ethnology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / secondary
  • Prostatic Neoplasms / surgery
  • RNA Interference
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • SOS1 Protein / genetics
  • SOS1 Protein / metabolism*
  • Time Factors
  • Tissue Array Analysis
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • SOS1 Protein
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3