Abstract
Abstract Aging is the number one risk factor for breast cancer development. Increasing evidence suggests the potential of mammary stem cells (MaSCs) and their progenitors to generate certain types of breast cancers through neoplastic transformation. Our previous study has shown increased percentage of MaSC-enriched basal cell population (Lin-CD49fhighCD24med) and increased MaSC frequency during aging in murine models. On the other hand, a recent study from another group showed an increased frequency of CD49fhigh cells in the human luminal population (CD227+) during aging, indicating possible aberrant expression of CD49f in the aged luminal cells. However, how these age-related luminal cells with basal markers are generated and how they contribute to potential breast cancer development remains unknown. Here we apply bioinformatics analysis on Next Generation Whole Transcriptome Sequencing data of MaSC-enriched basal cell population (Lin-CD49fhighCD24med) and luminal progenitor-enriched cell population (Lin-CD49flowCD24high) of both young (4 to 6 months) and old (26 to 31 months) mouse mammary gland to test the hypothesis that age-associated increase of basal cell population and MaSCs may be due to the gain of basal cell markers and features by luminal cells. By Gene Set Enrichment Analysis (GSEA) we found a significant loss of basal cell and basal mammosphere signatures and a significant enrichment of luminal cell and luminal mammosphere signature in the old basal cell population and mammospheres in comparison with the young basal cell population and mammospheres. The core enrichment luminal genes from GSEA are able to cluster the old MaSC-enriched basal cell population as well as mammospheres closer to the cluster of luminal population than to the young basal population. These analyses indicate that aging may be associated with an expansion of aberrant MaSCs with both basal and luminal markers in mice, which may be the precursors of certain types of breast cancer. We are now studying the potential function of the basal-like luminal cells in the aged basal population. Citation Format: Gu X, Gao H, Wu A, Bandyopadhyay A, Dong Q, Sun L-Z. Transcriptome profiling reveals enrichment of luminal feature in aged basal cell population in murine mammary gland. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-04-03.
Published Version
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