Abstract 3868: Investigating biological mechanisms of breast cancer disparities: Basal-like specific gene expression
Authors: Meagan Grant, Christina Swoope, Christopher Walker, LiShann Ingram, Lori H. Neves, Melissa B. Davis
Journal: Cancer Research (2011)

Abstract Across all racial groups, breast cancer is the most common cancer diagnosed among women in the United States. While Caucasian women experience a higher rate of incidence of breast cancer, African American women suffer from a much greater mortality rate and have a higher rate of recurrence. This may be because African American women have a higher likelihood of developing an ER negative form of breast cancer, basal-like tumors. The purpose of this study was to determine if there is differential expression of 16 candidate oncogenes genes across different cancer subtypes. Cell lines derived from two breast cancer subtypes (ER + and basal-like) were examined and compared to a normal cell line in order to determine differential gene expression. Determining the subtype specificity of certain oncogenes is clinically significant in that this knowledge provides evidence of distinct etiology and therapeutic targets among subtypes. Knowing the subtype specificity of these genes could prove to be predictive of response to certain treatments and could allow for the identification of potential therapeutic targets. To select genes that were to be investigated, a spreadsheet of oncogene scores was consulted. Genes were selected based on oncogene rank; tumor suppressor rank and fold change between expressions in basal versus non-basal breast cancer. A preliminary gene list was uploaded into the Database for Annotation, Visualization, and Integrated Discovery (DAVID) so as to find enrichment of gene ontologies. RNA expression primers were designed for target genes using NCBI, Primer 3, and PrimerBlast. RT-PCR was used to detect the presence or absence of a transcript in each of the cell lines. qPCR was used to quantify the expression of the transcripts that were amplified by RT-PCR. Immunohistochemistry was used to visualize the distribution and localization of gene products. IL17RB, MBD6, VIPR1, ILGF, IRS-1, IGF2R, and TP53INP1 exhibited amplification in the cancer cell lines but not in normal cell lines. IGFBP6, GAL, LPIN1, ENPP1, ERBBX, and FGFR2 were expressed only in basal-like breast cancer cells. Quantification by qPCR showed IL17RB, ILGF, IRS-1, and IGF2R had higher expression in basal-like cancer than in ER + breast cancer. Conversely, VIPR1 exhibited higher expression in ER+ breast cancer than in basal-like cancer. Immunostaining performed with VIPR1, ERBBX, and IGFPB6 showed differential localization between cell lines. In ER + cells, VIPR1 and ERBBX are both nuclear. In basal-like cells VIPR1 is cytoplasmic, which suggests that it confers metastatic tendencies, and ERBBX experiences nuclear exclusion, which may be due to association with internal organelles such as the lysosomes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3868. doi:10.1158/1538-7445.AM2011-3868