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

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.

Sign in / Sign up

Export Citation Format

Share Document