Sterol dependent LDL-receptor gene transcription in lymphocytes from normal and CML patients

Cancer Letters
R GoelD Kaul

Abstract

Sterol regulatory element (SRE) has been recognized to regulate various key genes coding for especially low density lipoprotein (LDL)-receptor, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and HMG-CoA synthase known to play a crucial role in the cholesterol feedback mechanism. The deranged cholesterol feedback mechanism has been widely recognised in initiation as well as progression of various types of cancers including chronic myeloid leukaemia (CML). Consequently, the present study was addressed to understand this phenomenon and revealed the existence of a unique 47 kDa protein factor having affinity for this SRE sequence in lymphocytes from normal subjects as well as its absence in lymphocytes from untreated CML patients. However, this factor appeared when the CML patients achieved complete haematological remission (CHR) through alpha-interferon therapy. Further, an inverse relationship was also observed between sterol modulated LDL-receptor gene transcription and the binding affinity of this 47 kDa factor to the SRE sequence. Based upon these results we propose that alpha-interferon through its receptor initiates phosphatidic acid dependent signalling which in turn regulates the affinity of 47 kDa sterol regula...Continue Reading

References

Mar 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·H C StarkJ Weinberger
Apr 11, 1992·Nucleic Acids Research·S E Rutberg, Z Ronai
Sep 1, 1991·Trends in Biochemical Sciences·L M Pfeffer, Y H Tan
Feb 1, 1990·Nature·J L Goldstein, M S Brown
Oct 18, 1995·Molecular and Cellular Biochemistry·D KaulJ Singh

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Citations

Oct 15, 2003·Trends in Molecular Medicine·Deepak Kaul
May 19, 1998·Leukemia Research·R Goel, D Kaul
Jan 28, 1998·Leukemia Research·D Kaul, M Kaur
Jul 4, 1998·Leukemia Research·D Kaul
Jul 29, 1998·Leukemia Research·D Kaul, M Kaur

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