The tumor-selective over-expression of the human Hsp70 gene is attributed to the aberrant controls at both initiation and elongation levels of transcription.
The tumor selective over-expression of the human Hsp70 gene has been well documented in human tumors, linked to the poor prognosis, being refractory to chemo- and radio-therapies as well as the advanced stage of tumorous lesions in particular. However, both the nature and details of aberrations in the control of the Hsp70 expression in tumor remain enigmatic. By comparing various upstream segments of the Hsp70 gene for each's ability to drive the luciferase reporter genes in the context of the tumor cell lines varying in their p53 status and an immortal normal liver cell line, we demonstrated in a great detail the defects in the control mechanisms at the both initiation and elongation levels of transcription being instrumental to the tumor selective profile of its expression. Our data should not only offer new insights into our understanding of the tumor specific over-expression of the human Hsp70 gene, but also paved the way for the rational utilization of the tumor selective mechanism with the Hsp70 at the central stage for targeting the therapeutic gene expression to human tumors.
The State-key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, LN 25/2200, Xie-tu Road, Shanghai 200032, China.
Ling
L
Cai
Jing De
JD
Zhu
D020121:5' Untranslated Regions / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005809:Genes, Regulator / Q000235:genetics*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D024363:Transcription Initiation Site / Q000502:physiology; D035602:Transcriptional Elongation Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics
D020121:5' Untranslated Regions; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D035602:Transcriptional Elongation Factors; D016159:Tumor Suppressor Protein p53