Comparison of Functional Proteomic Analyses of Human Breast Cancer Cell Lines T47D and MCF7

Aka, Juliette A.; Lin, Sheng‐Xiang

doi:10.1371/journal.pone.0031532

Cited by 48 publications

(24 citation statements)

References 18 publications

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“…Furthermore, activation of the ERβ2 isoform results in ERβ2/ERα heterodimers that are targeted for proteasomal degradation [56]. It is noteworthy, then, that E 2 increases ERβ in T47D but not in MCF-7 or BT-474 [57] and the ER β:α ratio in T47D is reported to be greater than in MCF-7[53], [58] thus, suggesting that cell-specific differences in ER subtypes and other receptors may underlie differential HLA expression in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Activation of ERα Signaling Differentially Modulates IFN-γ Induced HLA-Class II Expression in Breast Cancer Cells

et al. 2014

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The coordinate regulation of HLA class II (HLA-II) is controlled by the class II transactivator, CIITA, and is crucial for the development of anti-tumor immunity. HLA-II in breast carcinoma is associated with increased IFN-γ levels, reduced expression of the estrogen receptor (ER) and reduced age at diagnosis. Here, we tested the hypothesis that estradiol (E2) and ERα signaling contribute to the regulation of IFN-γ inducible HLA-II in breast cancer cells. Using a panel of established ER− and ER+ breast cancer cell lines, we showed that E2 attenuated HLA-DR in two ER+ lines (MCF-7 and BT-474), but not in T47D, while it augmented expression in ER− lines, SK-BR-3 and MDA-MB-231. To further study the mechanism(s), we used paired transfectants: ERα+ MC2 (MDA-MB-231 c10A transfected with the wild type ERα gene) and ERα− VC5 (MDA-MB-231 c10A transfected with the empty vector), treated or not with E2 and IFN-γ. HLA-II and CIITA were severely reduced in MC2 compared to VC5 and were further exacerbated by E2 treatment. Reduced expression occurred at the level of the IFN-γ inducible CIITA promoter IV. The anti-estrogen ICI 182,780 and gene silencing with ESR1 siRNA reversed the E2 inhibitory effects, signifying an antagonistic role for activated ERα on CIITA pIV activity. Moreover, STAT1 signaling, necessary for CIITA pIV activation, and selected STAT1 regulated genes were variably downregulated by E2 in transfected and endogenous ERα positive breast cancer cells, whereas STAT1 signaling was noticeably augmented in ERα− breast cancer cells. Collectively, these results imply immune escape mechanisms in ERα+ breast cancer may be facilitated through an ERα suppressive mechanism on IFN-γ signaling.

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Section: Discussionmentioning

confidence: 99%

Activation of ERα Signaling Differentially Modulates IFN-γ Induced HLA-Class II Expression in Breast Cancer Cells

et al. 2014

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“…Though statins are known to inhibit cholesterol biosynthesis through mevalonate pathway, they may target multiple proteins regulating different pro survival pathways thereby inhibiting proliferation of cancer cells. Aka et al, recently compared a functional proteome of two hormone-dependent breast cancer cells lines MCF-7 and T47D and the analyses showed that 164 proteins involved in various proliferative functions are differentially expressed between them [8] . Lovastatin induces breast cancer cell death through modulation of E2F1-pathway by altering expression of prohibitin and retinoblastoma (Rb) proteins [9] .…”

Section: Introductionmentioning

confidence: 99%

Fluvastatin Mediated Breast Cancer Cell Death: A Proteomic Approach to Identify Differentially Regulated Proteins in MDA-MB-231 Cells

et al. 2014

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Statins are increasingly being recognized as anti-cancer agents against various cancers including breast cancer. To understand the molecular pathways targeted by fluvastatin and its differential sensitivity against metastatic breast cancer cells, we analyzed protein alterations in MDA-MB-231 cells treated with fluvastatin using 2-DE in combination with LC-MS/MS. Results revealed dys-regulation of 39 protein spots corresponding to 35 different proteins. To determine the relevance of altered protein profiles with breast cancer cell death, we mapped these proteins to major pathways involved in the regulation of cell-to-cell signaling and interaction, cell cycle, Rho GDI and proteasomal pathways using IPA analysis. Highly interconnected sub networks showed that vimentin and ERK1/2 proteins play a central role in controlling the expression of altered proteins. Fluvastatin treatment caused proteolysis of vimentin, a marker of epithelial to mesenchymal transition. This effect of fluvastatin was reversed in the presence of mevalonate, a downstream product of HMG-CoA and caspase-3 inhibitor. Interestingly, fluvastatin neither caused an appreciable cell death nor did modulate vimentin expression in normal mammary epithelial cells. In conclusion, fluvastatin alters levels of cytoskeletal proteins, primarily targeting vimentin through increased caspase-3- mediated proteolysis, thereby suggesting a role for vimentin in statin-induced breast cancer cell death.

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“…adherent cultured MCF-7 cells. Recently a proteomic analysis has been conducted for MCF-7 monolayer cells in comparison to another commonly used breast cancer cell line T-47D [29]. We believe this to be the first time that the proteome of multiple passages of MCF-7 spheres have been compared to monolayer cells.…”

Section: Discussionmentioning

confidence: 92%

Proteomic Comparison of MCF-7 Tumoursphere and Monolayer Cultures

et al. 2012

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Breast cancer is a heterogenous disease, composed of tumour cells with differing gene expressions and phenotypes. Very few antigens have been identified and a better understanding of tumour initiating-cells as targets for therapy is critically needed. Recently, a rare subpopulation of cells within tumours has been described with the ability to: (i) initiate and sustain tumour growth; (ii) resist traditional therapies and allow for secondary tumour dissemination; and (iii) display some of the characteristics of stem cells such as self-renewal. These cells are termed tumour-initiating cells or cancer stem cells, or alternatively, in the case of breast cancer, breast cancer stem cells. Previous studies have demonstrated that breast cancer stem cells can be enriched for in “tumoursphere” culture. Proteomics represents a novel way to investigate protein expression between cells. We hypothesise that characterisation of the proteome of the breast cancer line MCF-7 tumourspheres compared to adherent/differentiated cells identifies proteins of novel interest for further isolating or targeting breast cancer stem cells. We present evidence that: (i) the proteome of adherent cells is different to the proteome of cells grown in sphere medium from either early passage (passage 2) or late passage (passage 5) spheres; (ii) that spheres are enriched in expression of a variety of tumour-relevant proteins (including MUC1 and Galectin-3); and (iii) that targeting of one of these identified proteins (galectin-3) using an inhibitor (N-acetyllactosamine) decreases sphere formation/self-renewal of MCF-7 cancer stem cells in vitro and tumourigenicity in vivo. Hence, proteomic analysis of tumourspheres may find use in identifying novel targets for future therapy. The therapeutic targeting of breast cancer stem cells, a highly clinically relevant sub-population of tumour cells, has the potential to eliminate residual disease and may become an important component of a multi-modality treatment of cancer.

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Comparison of Functional Proteomic Analyses of Human Breast Cancer Cell Lines T47D and MCF7

Cited by 48 publications

References 18 publications

Activation of ERα Signaling Differentially Modulates IFN-γ Induced HLA-Class II Expression in Breast Cancer Cells

Activation of ERα Signaling Differentially Modulates IFN-γ Induced HLA-Class II Expression in Breast Cancer Cells

Fluvastatin Mediated Breast Cancer Cell Death: A Proteomic Approach to Identify Differentially Regulated Proteins in MDA-MB-231 Cells

Proteomic Comparison of MCF-7 Tumoursphere and Monolayer Cultures

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