Identifying signaling pathways involved in mammary gland development has contributed to our understanding of breast cancer. While growth of the gland is isometric between birth and puberty, ductal expansion is significant and morphological changes such as terminal end bud formation occur during this developmental window. While estrogen receptor alpha (ERá) and progesterone receptor (PR) expression are evident during this time, pre-pubertal levels of free estradiol are low and growth is independent of ovarian hormones. Basal-like breast cancers represent a subset of breast cancers (10-15% of all women with breast cancer) that often lack ERá, PR and HER2 (i.e. triple negative), are ovarian hormone independent, and have a worse prognosis than other tumor subtypes. Animal models for basal-like breast cancer are limited. Therefore identifying gene changes during prepubertal mammary gland development may give insight into the mechanisms that drive these breast cancers. Offspring from individual Sprague Dawley dams were sacrificed on postnatal days (PND) 2, 10 and 20 (n = 5 to 6 for each PND) and the fourth inguinal glands were removed. RNA was isolated and sequenced by RNASeq using 25 million paired end reads. Bioinformatics analysis utilizing TopHat, Bowtie2, and CummeRbund revealed >7000 genes that changed during this time (alpha = 0.05). Analysis by DAVID/KEGG and Ingenuity Pathway Analysis demonstrated differences in immune pathways over time whereby immune genes increased from PND 2 to 10 to 20. Specifically, T Cell Receptor Signaling and B Cell Development were two of the most affected pathways. These results are interesting as recent studies have indicated that the immune system may influence basal-like breast cancers. Molecular signatures defining subtypes of basal-like breast cancer have been described and include basal-like immunosuppressed (BLIS) and basal-like immune activated (BLIA). A better understanding of the role of the immune system in prepubertal mammary gland development may help guide treatment strategies for hormone independent breast cancers.
Citation Format: Hillary Stires, Catina Crismale-Gann, William J. Belden, Wendie S. Cohick. The prepubertal mammary gland transcriptome suggests a role for the immune system in hormone-independent breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 785.