Molecular basis of cholesterol feedback lesion in CNS tumours.
An important feature of malignant transformation of tumours is the loss of cholesterol feedback inhibition mechanism (cholesterol-feedback lesion) that regulates mevalonate pathway recognized to play a crucial role in cellular growth, death and differentiation. Recently, it was shown that Receptor-C(k)-dependent signalling regulates genes involved in maintaining cellular cholesterol homeostasis through a transcription factor sterol response element binding protein (SREBP) having affinity for sterol regulatory element (SRE) present in the promoter region of these genes. The present study revealed that CNS tumours exhibit overexpression of Receptor-C(k) gene product which was accompanied by their inability to express SREBP gene product and this phenomenon has the inherent capacity to initiate the cholesterol feedback lesion in these tumours. Based upon these and our earlier studies, we propose for the first time that this loss of cholesterol feedback control may be responsible for the initiation of these tumours.
Kaul
D
D
Department of Experimental Medicine, Biotechnology and Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
Khosla
V K
VK
D000328:Adult; D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins; D016543:Central Nervous System Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D018110:Receptors, Lipoprotein; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; C113493:receptor-Ck; D002784:Cholesterol