Gene expression analysis of drug-resistant MCF-7 cells: implications for relation to extracellular matrix proteins

2009 ◽  
Vol 65 (3) ◽  
pp. 447-455 ◽  
Author(s):  
Özlem Darcansoy Işeri ◽  
Meltem Demirel Kars ◽  
Fikret Arpaci ◽  
Ufuk Gündüz
2001 ◽  
Vol 12 (11) ◽  
pp. 2300-2309 ◽  
Author(s):  
CHRISTIAN MORATH ◽  
CLAUDIUS DECHOW ◽  
INGO LEHRKE ◽  
VOLKER HAXSEN ◽  
RÜDIGER WALDHERR ◽  
...  

Abstract. Transforming growth factor—β1 (TGF-β1) overexpression plays a key role in the glomerular accumulation of extracellular matrix proteins in renal disease. Retinoids have previously been shown to significantly limit glomerular damage in rat experimental glomerulonephritis. Therefore, the effects of all-trans retinoic acid and isotretinoin on the components of the TGF-β system and extracellular matrix proteins in anti-Thy1.1-nephritis (Thy-GN) were investigated. Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of 10 mg/kg body wt all-trans retinoic acid or 40 mg/kg body wt isotretinoin (n= 9 per group) either with a pretreatment (day -2 through 8) or posttreatment protocol (day +3 through 8),i.e., starting before or after induction of Thy-GN, respectively. Urinary TGF-β1 excretion was 60% lower in all-trans retinoic acid-treated animals with Thy-GN (P< 0.025). The increase of cortical TGF-β1 gene expression in Thy-GN rats was significantly attenuated with all-trans retinoic acid and even more with isotretinoin treatment as compared with untreated animals (P< 0.025). Cortical expression of TGF receptor II, but not receptor I gene expression, was significantly lower in animals treated with all-trans retinoic acid or isotretinoin (P< 0.05). In all-trans retinoic acid—treated animals with Thy-GN, the increase of glomerular TGF-β1 protein (P< 0.008) and TGF-β1 (P< 0.025) and TGF receptor II mRNA (P< 0.015) was significantly less. Immunohistochemistry revealed less glomerular staining for TGF-β1 and TGF receptor II in the presence of all-trans retinoic acid. TGF-β1 immunostaining was not restricted to monocytes and macrophages, as indicated by double-staining. Glomerular staining for collagen IV and collagen III was less in animals treated with isotretinoin (P< 0.02 for both) in contrast to all-trans retinoic acid, whereas fibronectin remained unchanged. It was concluded that the beneficial effects of retinoids on glomerular damage are presumably due to a marked reduction in renal TGF-β1 and TGF receptor II expression.


RNA Biology ◽  
2019 ◽  
Vol 16 (5) ◽  
pp. 661-674 ◽  
Author(s):  
Martin Porsch ◽  
Esra Özdemir ◽  
Martin Wisniewski ◽  
Sebastian Graf ◽  
Fabian Bull ◽  
...  

2004 ◽  
Vol 74 (2) ◽  
pp. 187-193 ◽  
Author(s):  
Kenji Takahashi ◽  
Masashi Yamazaki ◽  
Takashi Saisu ◽  
Arata Nakajima ◽  
Sumito Shimizu ◽  
...  

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258363
Author(s):  
Ola D. A. Shammout ◽  
Naglaa S. Ashmawy ◽  
Sarra B. Shakartalla ◽  
Alaa M. Altaie ◽  
Mohammad H. Semreen ◽  
...  

Drug resistance is responsible for the failure of many available anticancer drugs. Several studies have demonstrated the association between the alteration in sphingolipids (SPLs) and the development of drug resistance. To investigate the association between SPLs metabolism and doxorubicin (dox)-resistance in MCF-7 cells, a comparative sphingolipidomics analysis between dox-sensitive (parental) and -resistant MCF-7 cell lines along with validation by gene expression analysis were conducted. A total of 31 SPLs representing 5 subcategories were identified. The data obtained revealed that SPLs were clustered into two groups differentiating parental from dox-resistant cells. Eight SPLs were significantly altered in response to dox-resistance including SM (d18:1/16), SM (d18:1/24:2), SM (d18:1/24:0), SM (d18:1/20:0), SM (d18:1/23:1), HexCer (d18:1/24:0), SM (d18:1/15:0), DHSM (d18:0/20:0). The current study is the first to conclusively ascertain the potential involvement of dysregulated SPLs in dox-resistance in MCF-7 cells. SPLs metabolism in dox-resistant MCF-7 cells is oriented toward the downregulation of ceramides (Cer) and the concomitant increase in sphingomyelin (SM). Gene expression analysis has revealed that dox-resistant cells tend to escape from the Cer-related apoptosis by the activation of SM-Cer and GluCer-LacCer-ganglioside pathways. The enzymes that were correlated to the alteration in SPLs metabolism of dox-resistant MCF-7 cells and significantly altered in gene expression can represent potential targets that can represent a winning strategy for the future development of promising anticancer drugs.


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