Investigation of the Link Between Prolactin, Mammary Gland Development and Carcinogenesis by Transcript Profiling

摘要

Mammary lobuloalveolar development during pregnancy is controlled by the endocrine action of prolactin, estrogen and progesterone, but currently little is known of the transcriptional events that occur in response to these hormones. This study examines the transcriptional response of the mammary gland to the direct action of prolactin. Mammary tissue recombination experiments demonstrated that lobuloalveolar development is dependent upon the presence of prolactin receptors in mammary epithelium but not the stroma. Comparison of transcript profiles derived from recombined glands with and without epithelial prolactin receptors, from glands without epithelium, and from SCp2 cells treated with and without prolactin, allowed a small set of epithelial-specific prolactin-modulated transcripts to be identified. This included the epithelial specific Ets transcription factor Elf5. Elf5 expression decreased in Prlr(+/-) mammary glands but there was no change in Prlr expression in Elf5(+/-) mammary glands, indicate that ElfS acts downstream of prolactin. The expression of milk protein genes decreased in both Prlr(+/-) and Elf5(+/-) mammary glands, consistent with a role for Elf5 in mediating prolactin-induced epithelial differentiation, however, the expression of a number of growth factors decreased in Prlr(+/-) mammary glands but increased in Elf5(+/-) mammary glands. Thus prolactin induces the expression of Elf5, which performs a pivotal role in mediating the switch from prolactin induced epithelial cell proliferation to differentiation within the mammary gland during pregnancy.