scholarly journals Potential role of transforming growth factor beta1 in drug resistance of tumor cells.

2003 ◽  
Vol 50 (2) ◽  
pp. 497-508 ◽  
Author(s):  
Rostyslav Stoika ◽  
Mariya Yakymovych ◽  
Serhiy Souchelnytskyi ◽  
Ihor Yakymovych
Keyword(s):  
Signal Transduction ◽  
Drug Resistance ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Signal Transduction Pathway ◽  
Target Cells ◽  
Type I ◽  
Transduction Pathway ◽  
L1210 Cells ◽  
Anti Cancer

Acquired drug resistance of tumor cells is frequently observed in cancer patients undergoing chemotherapy. We studied murine leukemia L1210 cells sensitive and resistant to the cytotoxic action of cisplatin and showed that cisplatin-resistant leukemia cells were also refractory to TGF beta1-dependent growth inhibition and apoptosis. Addressing the question about the mechanisms responsible for the cross-resistance to cisplatin and TGF beta1, we found that cisplatin- and TGF beta1-resistant L1210 cells possessed a decreased expression of type I TGF beta1 receptor, while the expression of type II TGF beta1 receptor was not affected. Western blot analysis of Smad proteins 2, 3, 4, 6, and 7, which participate in signal transduction pathway down-stream of the TGF beta1 receptors, revealed an increased expression of Smad 6, inhibiting TGF beta1 action, only in cisplatin- and TGF beta1-resistant L1210 cells. TGF beta1 and especially the cytotoxic mistletoe agglutinin increased Smad 6 expression in TGF beta1-sensitive but not in TGF beta1-resistant L1210 cells. TGF beta1-resistant L1210 cells also differed from TGF beta1-sensitive cells by the lack of expression of the pro-apoptotic p53 protein and higher level of expression of the anti-apoptotic Bcl-2 protein. Thus, the described co-expression of tumor cell refractoriness to an anti-cancer drug and to the inhibitory cytokine TGF beta1 is accompanied by multiple changes in the TGF beta1 signal transduction pathway and in other regulatory systems of the target cells. Besides, we found that various anti-tumor drugs and cytotoxic plant lectins increased the level of TGF beta1 expression in both TGFbeta1-sensitive and -resistant L1210 cells. A hypothesis is proposed that TGFbeta1 can at least partly mediate the effect of cell-stressing agents and, thus, the development of TGF beta1 resistance may be responsible for the appearance of tumor cell refractoriness to the action of some anti-cancer drugs.

scholarly journals Differentially Regulated Interferon Response Determines the Outcome of Newcastle Disease Virus Infection in Normal and Tumor Cell Lines

2006 ◽  
Vol 80 (11) ◽  
pp. 5145-5155 ◽  
Author(s):  
Sateesh Krishnamurthy ◽  
Toru Takimoto ◽  
Ruth Ann Scroggs ◽  
Allen Portner
Keyword(s):  
Signal Transduction ◽  
Tumor Cell ◽  
Newcastle Disease Virus ◽  
Tumor Cells ◽  
Disease Virus ◽  
Cell Lines ◽  
Newcastle Disease ◽  
Signal Transduction Pathway ◽  
Tumor Cell Lines ◽  
Transduction Pathway

ABSTRACT Newcastle disease virus (NDV) is a negative-strand RNA virus with oncolytic activity against human tumors. Its effectiveness against tumors and safety in normal tissue have been demonstrated in several clinical studies. Here we show that the spread of NDV infection is drastically different in normal cell lines than in tumor cell lines and that the two cell types respond differently to beta interferon (IFN-β) treatment. NDV rapidly replicated and killed HT-1080 human fibrosarcoma cells but spread poorly in CCD-1122Sk human skin fibroblast cells. Pretreatment with endogenous or exogenous IFN-β completely inhibited NDV replication in normal cells but had little or no effect in tumor cells. Thus, the outcome of NDV infection appeared to depend on the response of uninfected cells to IFN-β. To investigate their differences in IFN responsiveness, we analyzed and compared the expression and activation of components of the IFN signal transduction pathway in these two types of cells. The levels of phosphorylated STAT1 and STAT2 and that of the ISGF3 complex were markedly reduced in IFN-β-treated tumor cells. Moreover, cDNA microarray analysis revealed significantly fewer IFN-regulated genes in the HT-1080 cells than in the CDD-1122Sk cells. This finding suggests that tumor cells demonstrate a less-than-optimum antiviral response because of a lesion in their IFN signal transduction pathway. The rapid spread of NDV in HT-1080 cells appears to be caused by their deficient expression of anti-NDV proteins upon exposure to IFN-β.

scholarly journals Myostatin Signals through a Transforming Growth Factor β-Like Signaling Pathway To Block Adipogenesis

2003 ◽  
Vol 23 (20) ◽  
pp. 7230-7242 ◽  
Author(s):  
A. Rebbapragada ◽  
H. Benchabane ◽  
J. L. Wrana ◽  
A. J. Celeste ◽  
L. Attisano
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Signal Transduction Pathway ◽  
Transforming Growth Factor Β ◽  
Negative Regulator ◽  
Type I ◽  
Type Ii ◽  
Transduction Pathway

ABSTRACT Myostatin, a transforming growth factor β (TGF-β) family member, is a potent negative regulator of skeletal muscle growth. In this study we characterized the myostatin signal transduction pathway and examined its effect on bone morphogenetic protein (BMP)-induced adipogenesis. While both BMP7 and BMP2 activated transcription from the BMP-responsive I-BRE-Lux reporter and induced adipogenic differentiation, myostatin inhibited BMP7- but not BMP2-mediated responses. To dissect the molecular mechanism of this antagonism, we characterized the myostatin signal transduction pathway. We showed that myostatin binds the type II Ser/Thr kinase receptor. ActRIIB, and then partners with a type I receptor, either activin receptor-like kinase 4 (ALK4 or ActRIB) or ALK5 (TβRI), to induce phosphorylation of Smad2/Smad3 and activate a TGF-β-like signaling pathway. We demonstrated that myostatin prevents BMP7 but not BMP2 binding to its receptors and that BMP7-induced heteromeric receptor complex formation is blocked by competition for the common type II receptor, ActRIIB. Thus, our results reveal a strikingly specific antagonism of BMP7-mediated processes by myostatin and suggest that myostatin is an important regulator of adipogenesis.

scholarly journals Wnt/β-catenin signal transduction pathway in prostate cancer and associated drug resistance

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chunyang Wang ◽  
Qi Chen ◽  
Huachao Xu
Keyword(s):  
Prostate Cancer ◽  
Signal Transduction ◽  
Drug Resistance ◽  
Androgen Receptor ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Cancer Pathogenesis ◽  
Asian Men ◽  
Therapy Development ◽  
The Impact

AbstractGlobally, prostate cancer ranks second in cancer burden of the men. It occurs more frequently in black men compared to white or Asian men. Usually, high rates exist for men aged 60 and above. In this review, we focus on the Wnt/β-catenin signal transduction pathway in prostate cancer since many studies have reported that β-catenin can function as an oncogene and is important in Wnt signaling. We also relate its expression to the androgen receptor and MMP-7 protein, both critical to prostate cancer pathogenesis. Some mutations in the androgen receptor also impact the androgen-β-catenin axis and hence, lead to the progression of prostate cancer. We have also reviewed MiRNAs that modulate this pathway in prostate cancer. Finally, we have summarized the impact of Wnt/β-catenin pathway proteins in the drug resistance of prostate cancer as it is a challenging facet of therapy development due to the complexity of signaling pathways interaction and cross-talk.

Expression Cloning and Signal Transduction Pathway of P2U Receptor in Mammary Tumor Cells

Neurosignals ◽  
1996 ◽  
Vol 5 (1) ◽  
pp. 9-21 ◽  
Author(s):  
Koh-ichi Enomoto ◽  
Kishio Furuya ◽  
Robert C. Moore ◽  
Shunichi Yamagishi ◽  
Takami Oka ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Tumor Cells ◽  
Mammary Tumor ◽  
Signal Transduction Pathway ◽  
Expression Cloning ◽  
Transduction Pathway ◽  
Mammary Tumor Cells
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