Regulation of cellular communication network factor 2 (CCN2) in breast cancer cells via the cell-type dependent interplay between CCN2 and glycolysis

Karanjin, an abundantly occurring furanoflavonoid in edible and non-edible legumes, exerts diverse biological effects in vivo, and in vitro. Its potential as an anticancer agent is also gaining traction following recent demonstrations of its anti-proliferative, cell cycle inhibitory, and pro-apoptotic effects. However, the universality of its anticancer potential is yet to be scrutinized, particularly so because flavonoids can act as selective estrogen receptor modulators (SERMs). Even the genomic correlates of its biological activities are yet to be examined in hormone responsive cells. This paper presents the early and direct transcriptomic footprint of 10 μM karanjin in MCF-7 breast cancer cells, using next generation sequencing technology (RNA-seq). We show that karanjin-modulated gene-expression repertoire is enriched in several hallmark gene sets, which include early estrogen-response, and G2/M checkpoint genes. Genes modulated by karanjin overlapped with those modulated by 1 nM 17β-estradiol (E2), or 1 μM tamoxifen. Karanjin altered the expression of selected estrogen-regulated genes in a cell-type, and concentration dependent manner. It downmodulated the expression of ERα protein in MCF-7 cells. Furthermore, ERα knockdown negatively impacted karanjins ability to modulate the expression of selected E2 target genes. Our data suggest that karanjin exerts its effects on ERα-positive breast cancer cells, at least in part, via ERα. The apparent SERM-like effects of karanjin pose a caveat to the anticancer potential of karanjin. In-depth studies on cell-type and concentration-dependent effects of karanjin may bring out its true potential in endocrine therapies.

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Exchange of microRNAs between Breast Cancer Cells and Bone Marrow Stroma: Potential for Avenues To Revisit Hematopoietic Stem Cell Transplantation for Breast and Other Cancers That Show Preference for Bone Marrow.

Blood ◽

10.1182/blood.v110.11.1199.1199 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1199-1199

Author(s):

Marcelo Taborga ◽

Pranela Rameshwar

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Gap Junctions ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cancer Metastasis ◽

Luciferase Activity ◽

Bone Marrow Stroma ◽

Cell Type ◽

Marrow Stroma

Abstract Previous failure of autologous bone marrow transplantation as a viable treatment of breast cancer opens the field for investigational studies since the bone marrow, as a source of cancer metastasis, remains a clinical dilemma. This study hypothesizes that a subset of breast cancer cells enter the bone marrow at an early period of disease development, perhaps prior to clinical detection, where they evade chemotherapeutic damage even at high doses. An understanding of this cell population might be crucial for the future success of bone marrow transplants in patients suffering from breast cancer metastasis to the bone marrow. In vivo and in vitro studies have demonstrated gap junctions between bone marrow stroma and breast cancer cells. The gap junctions can passage CFDA cell tracer between stroma and cancer cells. This exchange can be blocked by the gap junctional intercellular communication inhibitor, 1-Octanol, suggesting functional gap junctions. We have now implemented quantitative studies to determine the role of specific microRNAs (miRNAs) in blunting of mRNA translation of the Tac1 gene in cancer cells. The first set of studies optimized the effects of miRNAs, 130a and 206 in the suppression of Tac1 mRNA in the low invasive T47D and the aggressive MDA-MB-231 breast cancer cell lines. The miRNAs were transfected into cells containing the pMIR-R/Tac1/SG vector, which includes the 3′ UTR of Tac1 mRNA. Luciferase activity in cell lysates showed synergism between the two miRNAs, indicating that the predicted miRNAs can inhibit Tac1 translation. The next set of studies determined whether miRNAs 130a and 206 can cross gap junctions between stroma and cancer cells to suppress Tac1 mRNA. The miRNAs were transfected in one cell type and pMIR-R/Tac1/SG in the other cell type. Luciferase activity and parallel studies with 1-Octanol verified movement of miRNAs via the gap junction. These studies recapitulate the downregulation of endogenous Tac1 and other cytokines in the cancer cells. In summary, this study shows a role for miRNA exchange, between bone marrow stroma and breast cancer cells, as a mechanism by which the cancer cells might evade detection and current methods of treatment. An understanding of these mechanisms might lead to new methods to remove cancer from bone marrow in future therapies.

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STI571 sensitizes breast cancer cells to 5-fluorouracil, cisplatin and camptothecin in a cell type-specific manner

Biochemical Pharmacology ◽

10.1016/j.bcp.2009.04.007 ◽

2009 ◽

Vol 78 (3) ◽

pp. 249-260 ◽

Cited By ~ 20

Author(s):

Jonathan T. Sims ◽

Sourik Ganguly ◽

Leann S. Fiore ◽

Chris J. Holler ◽

Eun-Sil Park ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cell Type ◽

Specific Manner ◽

A Cell ◽

Cell Type Specific

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Cell Type and Culture Condition–Dependent Alternative Splicing in Human Breast Cancer Cells Revealed by Splicing-Sensitive Microarrays

Cancer Research ◽

10.1158/0008-5472.can-05-2593 ◽

2006 ◽

Vol 66 (4) ◽

pp. 1990-1999 ◽

Cited By ~ 50

Author(s):

Chunxia Li ◽

Mitsuo Kato ◽

Lily Shiue ◽

John E. Shively ◽

Manuel Ares ◽

...

Keyword(s):

Breast Cancer ◽

Alternative Splicing ◽

Cancer Cells ◽

Culture Condition ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Cell Type

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Cell-type specific regulation of human interstitial collagenase-1 gene expression by interleukin-1β (IL-1β) in human fibroblasts and BC-8701 breast cancer cells

Journal of Cellular Biochemistry ◽

10.1002/(sici)1097-4644(19970901)66:3<322::aid-jcb5>3.0.co;2-r ◽

1997 ◽

Vol 66 (3) ◽

pp. 322-336 ◽

Cited By ~ 75

Author(s):

Joni L. Rutter ◽

Ulrike Benbow ◽

Charles I. Coon ◽

Constance E. Brinckerhoff

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Human Fibroblasts ◽

Interleukin 1Β ◽

Cell Type ◽

Cell Type Specific ◽

Specific Regulation ◽

Interstitial Collagenase

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Telomerase downregulation induces proapoptotic genes expression and initializes breast cancer cells apoptosis followed by DNA fragmentation in a cell type dependent manner

Molecular Biology Reports ◽

10.1007/s11033-013-2600-9 ◽

2013 ◽

Vol 40 (8) ◽

pp. 4995-5004 ◽

Cited By ~ 11

Author(s):

Blazej Rubis ◽

Hanna Holysz ◽

Marta Gladych ◽

Ewa Toton ◽

Anna Paszel ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Dna Fragmentation ◽

Breast Cancer Cells ◽

Dependent Manner ◽

Cell Type ◽

Genes Expression ◽

A Cell

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Genome-Wide Progesterone Receptor Binding: Cell Type-Specific and Shared Mechanisms in T47D Breast Cancer Cells and Primary Leiomyoma Cells

PLoS ONE ◽

10.1371/journal.pone.0029021 ◽

2012 ◽

Vol 7 (1) ◽

pp. e29021 ◽

Cited By ~ 58

Author(s):

Ping Yin ◽

Damian Roqueiro ◽

Lei Huang ◽

Jonas K. Owen ◽

Anna Xie ◽

...

Keyword(s):

Breast Cancer ◽

Progesterone Receptor ◽

Cancer Cells ◽

Receptor Binding ◽

Breast Cancer Cells ◽

Cell Type ◽

Genome Wide ◽

Cell Type Specific ◽

Binding Cell

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RANK-C Expression Sensitizes ER-Negative, EGFR-Positive Breast Cancer Cells to EGFR-Tyrosine Kinase Inhibitors (TKIs)

Genes ◽

10.3390/genes12111686 ◽

2021 ◽

Vol 12 (11) ◽

pp. 1686

Author(s):

Chaido Sirinian ◽

Anastasios D. Papanastasiou ◽

Soren E. Degn ◽

Theodora Frantzi ◽

Christos Aronis ◽

...

Keyword(s):

Breast Cancer ◽

Tyrosine Kinase ◽

Cancer Cells ◽

Colony Formation ◽

Breast Cancer Cells ◽

Kinase Inhibitors ◽

C Cells ◽

Cell Type ◽

A Cell ◽

Cell Type Specific

Background: We have previously shown that overexpression of RANK-c in ER-negative breast cancer cell lines attenuates aggressive properties of cancer cells, partially through a RANK-c /EGFR interaction. EGFR inhibition through TKIs in breast cancer has been tested in triple-negative disease settings with limited clinical benefit for patients. Here we test if expression of RANK-c in ER-negative breast cancer cells in conjunction with treatment with TK inhibitors (erlotinib or gefitinib) can affect survival and colony-forming capacity of cancer cells. Methods: Stably expressing MDA-MB-231-RANK-c and SKBR3-RANK-c cells were employed to test proliferation and colony formation in the presence of TKIs. In addition, Western blot analysis was performed to dissect EGFR related signaling cascades upon TK inhibition in the presence of RANK-c. Results: Interestingly the two RANK-c expressing, ER-negative cells lines presented with a distinct phenotype concerning TKI sensitivity upon treatment. MDA-MB-231-RANK-c cells had a higher sensitivity upon gefitinib treatment, while erlotinib decreased the proliferation rate of SKBR3-RANK-c cells. Further, colony formation assays for MDA-MB-231-RANK-c cells showed a decrease in the number and size of colonies developed in the presence of erlotinib. In addition, RANK-c seems to alter signaling through EGFR after TKI treatment in a cell type-specific manner. Conclusions: Our results indicate that ER-negative breast cancer cells that express RANK-c alter their sensitivity profile against tyrosine kinase inhibitors (erlotinib and gefitinib) in a cell type-specific and culture substrate-dependent manner.

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