The antiproliferative effects of progestins in T47D breast cancer cells are tempered by progestin induction of the ETS transcription factor Elf5.
Prolactin and progesterone act together to regulate mammary alveolar development, and both hormones have been implicated in breast cancer initiation and progression. Here we show that Elf5, a prolactin-induced ETS transcription factor that specifies the mammary secretory cell lineage, is also induced by progestins in breast cancer cells via a direct mechanism. To define the transcriptional response to progestin elicited via Elf5, we made an inducible Elf5 short hairpin-RNA knock-down model in T47D breast cancer cells and used it to prevent the progestin-induction of Elf5. Functional analysis of Affymetrix gene expression data using Gene Ontologies and Gene Set Enrichment Analysis showed enhancement of the progestin effects on cell cycle gene expression. Cell proliferation assays showed a more efficacious progestin-induced growth arrest when Elf5 was kept at baseline levels. These results showed that progestin induction of Elf5 expression tempered the antiproliferative effects of progestins in T47D cells, providing a further mechanistic link between prolactin and progestin in the regulation of mammary cell phenotype.
Cancer Research Program, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
H N
HN
Hilton
M
M
Kalyuga
M J
MJ
Cowley
M C
MC
Alles
H J
HJ
Lee
C E
CE
Caldon
K
K
Blazek
W
W
Kaplan
E A
EA
Musgrove
R J
RJ
Daly
M J
MJ
Naylor
J D
JD
Graham
C L
CL
Clarke
C J
CJ
Ormandy
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D011372:Progestins / Q000494:pharmacology* / Q000627:therapeutic use*; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism*; D034622:RNA Interference; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C116038:ELF5 protein, human; D011372:Progestins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D015735:Mifepristone