PTHrP P3 promoter activity in breast cancer cell lines: role of Ets1 and CBP (CREB binding protein).
Parathyroid hormone-related protein (PTHrP) is produced by many tumors including breast cancer. We have reported that Ets1 factor activates P3 PTHrP promoter in our model of tumorigenic breast cancer cell and not in pre- or non-tumorigenic cell lines, thus contributing to an increased PTHrP production. In this study, gel retardation assays revealed that Etsl and its promoter binding site (EBS) specifically formed complexes whose abundance correlates with Ets1 levels in the three cell lines. Coexpression of Etsl and CBP induced a synergistic activation of the P3 promoter only in the tumorigenic cell line. This synergism required the integrity of the EBS and was abrogated by E1A. All breast cancer cell lines showed high basal concentrations of phosphorylated CREB. Moreover a CRE-like sequence was also required for Ets1/CBP synergy and, finally, CREB expression was found to enhance the PTHrP P3 promoter activity. Thus a multipartite complex of transcription factors and coactivators seems to regulate PTHrP transcription and contribute to the alterations that promote tumorigenic behavior in breast epithelial cells.
Hamzaoui
Hinda
H
Institut Cochin, Université Paris Descartes, CNRS, (UMR 8104), France.
Rizk-Rabin
Marthe
M
Gordon
Jonthan
J
Offutt
Carlos
C
Bertherat
Jérôme
J
Bouizar
Zhor
Z
D017500:Adenovirus E1A Proteins / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics*; D050882:CREB-Binding Protein / Q000378:metabolism*; D045744:Cell Line, Tumor; D002645:Chickens; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics
D017500:Adenovirus E1A Proteins; C494041:ETS1 protein, human; D044162:Parathyroid Hormone-Related Protein; D050784:Proto-Oncogene Protein c-ets-1; D050882:CREB-Binding Protein; C494363:CREBBP protein, human