Project description:The ets transcription factor ELF5 specifies the differentiation of mammary progenitor cells to establish the milk-secreting lineage. ER- and poor prognosis basal breast cancers arise from this progenitor cell and these cancers express high levels of Elf5. Knockdown of ELF5 expression in basal breast cancer cell lines, or forced expression in luminal breast cancer cell lines, resulted in reduced cell proliferation. Transcript profiling and chromatin immunoprecipitation revealed that the transcriptional activity of ELF5 specified the gene expression patterns that distinguish basal from luminal breast cancer, including suppression of FOXA1, GATA3 and ER, key estrogen-action genes. Tamoxifen treatment of luminal MCF7 cells upregulated Elf5 expression and cells that acquired resistance to Tamoxifen became dependent on ELF5 for proliferation. ELF5 is a regulator of breast cancer cell proliferation, transcriptionally specifies the basal molecular subtype and is utilised by ER+ breast cancer cells to escape proliferative arrest caused by Tamoxifen. ChIP-Seq using an antibody to ELF5, in T47D breast carcinoma cell lines
Project description:About 15-20% of all breast cancers are triple negative breast cancers, which are often highly aggressive. We performed global quantitative phosphotyrosine profiling of a large panel of triple negative breast cancer cell lines using high resolution Fourier transform mass spectrometry. Our study identified 1,903 tyrosine-phosphorylated peptides derived from 969 proteins. Heterogeneous activation of tyrosine kinases was observed in triple negative breast cancer derived cell lines.
Project description:As part of the RATHER (RAtional THERapy for breast cancer: individualized treatment for difficult-to-treat breast cancer subtypes) consortium, expression profiling of 144 untreated primary invasive lobular carcinoma (ILC) breast cancer tissues and 15 ILC cell lines was performed using microarray. Gene expression profiling of 144 ILC breast cancers and 15 ILC cell lines
Project description:The ets transcription factor ELF5 specifies the differentiation of mammary progenitor cells to establish the milk-secreting lineage. ER- and poor prognosis basal breast cancers arise from this progenitor cell and these cancers express high levels of Elf5. Knockdown of ELF5 expression in basal breast cancer cell lines, or forced expression in luminal breast cancer cell lines, resulted in reduced cell proliferation. Transcript profiling and chromatin immunoprecipitation revealed that the transcriptional activity of ELF5 specified the gene expression patterns that distinguish basal from luminal breast cancer, including suppression of FOXA1, GATA3 and ER, key estrogen-action genes. Tamoxifen treatment of luminal MCF7 cells upregulated Elf5 expression and cells that acquired resistance to Tamoxifen became dependent on ELF5 for proliferation. ELF5 is a regulator of breast cancer cell proliferation, transcriptionally specifies the basal molecular subtype and is utilised by ER+ breast cancer cells to escape proliferative arrest caused by Tamoxifen.
Project description:Background: In previous work we discovered that T lymphocytes play a prominent role in the rise of brain metastases of ER-negative breast cancers. In the present study we explored expressional changes due to T cell contact associated with penetration through the BBB for breast cancer cell lines derived from cancers with various affinities for brain. Methods: Differential expression of proteins was identified by comparing the proteomes of the breast cancer cells before and after co-culture with T cells by using liquid chromatography-mass spectrometry (LC-MS). siRNA was used to silence protein expression in the tumor cells and the artificial BBB model was employed to study the effects on passage of the breast carcinoma cell lines. Results: Mass spectrometry-based proteomics revealed significant alterations in the expression of 35 proteins by the breast cancer cell lines upon T cell contact. Among the proteins is coronin-1A, a protein related to cell motility. Knockdown of CORO1A in the breast cancer cells reduced their ability to cross the artificial BBB to 60%. The effects were significantly less for the cell line derived from breast cancer with affinity for brain. The expression of coronin-1A was confirmed by immunohistochemistry and RT-PCR of 52 breast cancer samples of patients with metastasized breast cancers, with and without brain locations. Lastly, CORO1A upregulation was validated in a publicly available mRNA expression database from 204 primary breast cancers with known metastatic sites. Conclusions: We conclude that T lymphocytes trigger cancer cells to express proteins including coronin-1A thereby facilitating their passage through an in vitro BBB. In addition, a prominent role of coronin-1A in the formation of cerebral metastases in breast cancer patients is strongly suggestive by its upregulation in tissue samples of breast cancer patients with brain metastases.
Project description:The ets transcription factor ELF5 specifies the differentiation of mammary progenitor cells to establish the milk-secreting lineage. ER- and poor prognosis basal breast cancers arise from this progenitor cell and these cancers express high levels of Elf5. Knockdown of ELF5 expression in basal breast cancer cell lines, or forced expression in luminal breast cancer cell lines, resulted in reduced cell proliferation. Transcript profiling and chromatin immunoprecipitation revealed that the transcriptional activity of ELF5 specified the gene expression patterns that distinguish basal from luminal breast cancer, including suppression of FOXA1, GATA3 and ER, key estrogen-action genes. Tamoxifen treatment of luminal MCF7 cells upregulated Elf5 expression and cells that acquired resistance to Tamoxifen became dependent on ELF5 for proliferation. ELF5 is a regulator of breast cancer cell proliferation, transcriptionally specifies the basal molecular subtype and is utilised by ER+ breast cancer cells to escape proliferative arrest caused by Tamoxifen.
Project description:The ets transcription factor ELF5 specifies the differentiation of mammary progenitor cells to establish the milk-secreting lineage. ER- and poor prognosis basal breast cancers arise from this progenitor cell and these cancers express high levels of Elf5. Knockdown of ELF5 expression in basal breast cancer cell lines, or forced expression in luminal breast cancer cell lines, resulted in reduced cell proliferation. Transcript profiling and chromatin immunoprecipitation revealed that the transcriptional activity of ELF5 specified the gene expression patterns that distinguish basal from luminal breast cancer, including suppression of FOXA1, GATA3 and ER, key estrogen-action genes. Tamoxifen treatment of luminal MCF7 cells upregulated Elf5 expression and cells that acquired resistance to Tamoxifen became dependent on ELF5 for proliferation. ELF5 is a regulator of breast cancer cell proliferation, transcriptionally specifies the basal molecular subtype and is utilised by ER+ breast cancer cells to escape proliferative arrest caused by Tamoxifen.
Project description:The ets transcription factor ELF5 specifies the differentiation of mammary progenitor cells to establish the milk-secreting lineage. ER- and poor prognosis basal breast cancers arise from this progenitor cell and these cancers express high levels of Elf5. Knockdown of ELF5 expression in basal breast cancer cell lines, or forced expression in luminal breast cancer cell lines, resulted in reduced cell proliferation. Transcript profiling and chromatin immunoprecipitation revealed that the transcriptional activity of ELF5 specified the gene expression patterns that distinguish basal from luminal breast cancer, including suppression of FOXA1, GATA3 and ER, key estrogen-action genes. Tamoxifen treatment of luminal MCF7 cells upregulated Elf5 expression and cells that acquired resistance to Tamoxifen became dependent on ELF5 for proliferation. ELF5 is a regulator of breast cancer cell proliferation, transcriptionally specifies the basal molecular subtype and is utilised by ER+ breast cancer cells to escape proliferative arrest caused by Tamoxifen. Elf5 was knocked down via siRNA in basal HCC1937 cell lines, in triplicate. Elf5 was induced in luminal T47D and MCF7 cell lines via a doxycycline inducible expression vector, in duplicate.