Abrogation of TGFβ signaling induces apoptosis through the modulation of MAP kinase pathways in breast cancer cells

Lei, Xiufen; Yang, Junhua; Nichols, Robert W.; Sun, LuZhe

doi:10.1016/j.yexcr.2007.02.016

Cited by 21 publications

(30 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…6G). Additionally, we have previously shown that ectopic expression of a DNRII blocked TGF-␤ signaling and reduced the level of active ERK in the human MCF-7 breast cancer cell line, which contains a high level of autocrine TGF-␤ activity (40). Interestingly, we found that this DNRII-expressing MCF-7 cell line also has a lower level of the tyrosine-phosphorylated p52ShcA than the control vectortransfected cells (Fig.…”

Section: Shca Alters Role Of Tgf-␤ In Cellular Migration and Cell Grosupporting

confidence: 50%

Mutant p53 Disrupts Role of ShcA Protein in Balancing Smad Protein-dependent and -independent Signaling Activity of Transforming Growth Factor-β (TGF-β)

Lin

Yang

et al. 2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Section: Shca Alters Role Of Tgf-␤ In Cellular Migration and Cell Grosupporting

confidence: 50%

Mutant p53 Disrupts Role of ShcA Protein in Balancing Smad Protein-dependent and -independent Signaling Activity of Transforming Growth Factor-β (TGF-β)

Lin

Yang

et al. 2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

“…This effect of DSW appears to be mediated through TGF-β and Wnt5a signaling, subsequently resulting in the attenuated expression of CD44. TGF-β is one of the well known signaling pathways that are involved in the survival of breast cancer cells and cell migration (32). Moreover, abrogation of autocrine TGF-β signaling in MDA-MB-231 cells with transfection of a kinase-inactive type II TGF-β receptor impaired the basal migratory potential by blocking both Smad-dependent and -independent signaling pathways (33).…”

Section: Discussionmentioning

confidence: 99%

Mineral-enriched deep-sea water inhibits the metastatic potential of human breast cancer cell lines

Kim

Chun

Lee

et al. 2013

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Recently, the scientific community has begun to establish the health benefits of deep-sea water (DSW) due to its enrichment in nutrients and minerals. In this study, we investigated the effects of deep-sea water (DSW) on the metastatic potential of two human breast cancer cell lines exhibiting highly different phenotypes. MDA-MB-231 cells exhibit invasive/metastatic tumor features with rapid migration ability and high endogenous expression of TGF-β and Wnt5a. DSW treatment significantly inhibits their migratory ability in a wound-healing assay. This inhibitory effect of DSW appears to be mediated through TGF-β and Wnt5a signaling, resulting in attenuated expression of CD44. We further investigated the preventive effect of DSW on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced invasive/metastatic tumor features in non-invasive MCF-7 cells. Similar to the inhibitory effects shown in MDA-MB-231 cells, we observed that DSW treatment resulted in the inhibition of TPA-induced migration and MMP-9 activity with a concomitant decrease in mRNA levels of MMP-9, TGF-β, Wnt5a and Wnt3a. Taken together, our data show that DSW has inhibitory effects on breast cancer invasion/metastasis, suggesting that DSW has some promise in improving cancer survival by preventing tumor metastasis.

show abstract

“…Growth factor-regulated gene transcription and cell proliferation are blocked in mammalian cells when MAPK activity is inhibited (30)(31)(32), indicating that MAPKs are necessary for cell growth. Inhibition of ERK signaling using a MEK inhibitor, PD98059, induced apoptosis in MCF-7 cells (33,34). ERK activation was inversely correlated with apoptosis (35,36).…”

Section: Introductionmentioning

confidence: 99%

Role of PKC-ERK signaling in tamoxifen-induced apoptosis and tamoxifen resistance in human breast cancer cells

Xie

2012

Oncol Rep

View full text Add to dashboard Cite

Abstract. This study was designed to investigate the role of protein kinase C (PKC) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in tamoxifen (TAM)-induced apoptosis and drug resistance in human breast cancer cells. Drug-sensitive, or estrogen receptor (ER)-positive human breast carcinoma cells (MCF-7) and the multi-drug-resistant variant (ER-negative) MCF-7/ADR cells were treated with doses of TAM for various periods of time. Cell viability and apoptosis were assessed using cell counting, DNA fragmentation and flow cytometric analysis. We found that TAM administration caused a significant increase in apoptosis of MCF-7 cells but not MCF-7/ADR cells. Western blot analysis revealed enhanced expression of PKCδ but decreased expression of PKCα in ER-positive MCF-7 cells; while ER-negative MCF-7/ADR cells had decreased levels of PKCδ and increased levels of PKCα. Interestingly, we observed that in MCF-7 cells, TAM stimulated apoptosis by promoting rapid activation of PKCδ, antagonizing downstream signaling of ERK phosphorylation; while in MCF-7/ADR cells, TAM upregulated PKCα, which promoted ERK phosphorylation. These results suggest that PKCδ enhances apoptosis in TAM-treated MCF-7 cells by antagonizing ERK phosphorylation; while the PKCα pathway plays an important role in TAM-induced drug resistance by activating ERK signaling in MCF-7/ADR cells. The combination of TAM with PKCα and ERK inhibitors could promote TAM-induced apoptosis in breast cancer cells. IntroductionBreast cancer is a common malignancy in females and the second cause of death from cancer in women today (1). Treatment for breast cancer includes surgery, chemotherapy, radiotherapy and endocrine therapy. Tamoxifen (TAM), an antagonist of the estrogen receptor (ER), is a selective ER modulator (SERM). TAM is a front-line endocrine therapeutic drug for ER-positive breast cancers. Results from TAM therapy showed a 40-50% reduction in the risk of cancer recurrence and cancer mortality (2). Recently, TAM has been demonstrated to be effective for some ER-negative breast cancers, as well as other types of cancers, including gliomas. These data suggest that TAM may also be implicated in ER-independent antitumor mechanisms (3,4). Of note, some advanced breast cancers that initially respond well to TAM eventually become refractory to treatment (5-9). Thus, the traditional mechanism of TAM action through the ER is challenged, and other noncanonical pathways need to be explored.Protein kinase C (PKC), a family of serine/threonine kinases, is involved in many important cellular functions, including cell proliferation, migration, differentiation, and apoptosis (10-12). Twelve PKC isoforms have been discovered in various cell types, including conventional PKCs (cPKCα, βI/βII and γ), novel PKCs (nPKCδ, ε, η), and atypical PKCs (aPKCζ) (13,14). The expression of PKCα, δ, ε, η, γ, μ, and ζ has been detected in MCF-7 cells (15,16); PKCα is a marker for anti-estrogen resistance and is involved in the growth of TAM-resistant human breast cancer cell...

show abstract

Abrogation of TGFβ signaling induces apoptosis through the modulation of MAP kinase pathways in breast cancer cells

Cited by 21 publications

References 40 publications

Mutant p53 Disrupts Role of ShcA Protein in Balancing Smad Protein-dependent and -independent Signaling Activity of Transforming Growth Factor-β (TGF-β)

Mutant p53 Disrupts Role of ShcA Protein in Balancing Smad Protein-dependent and -independent Signaling Activity of Transforming Growth Factor-β (TGF-β)

Mineral-enriched deep-sea water inhibits the metastatic potential of human breast cancer cell lines

Role of PKC-ERK signaling in tamoxifen-induced apoptosis and tamoxifen resistance in human breast cancer cells

Contact Info

Product

Resources

About