Hypoxia induces class III beta-tubulin gene expression by HIF-1alpha binding to its 3' flanking region

Gene
Giuseppina RaspaglioCristiano Ferlini

Abstract

Class III beta-tubulin (TUBB3) overexpression represents a major mechanism of drug resistance to microtubule interacting agents such as taxanes and Vinca alkaloids. Here, we tested hypoxia as a possible inducer of TUBB3. The effects of hypoxia on TUBB3 expression were monitored at mRNA and protein level in A2780, in its paclitaxel-resistant counterpart (TC1) and in HeLa cells. Hypoxia was a strong inducer of TUBB3 in A2780, but not in TC1 and HeLa cells. In A2780 HIF-1alpha was knocked down using RNA interference and TUBB3 expression was assessed in normoxia and hypoxia. The silencing abolished the hypoxia-dependent increase of TUBB3, thereby demonstrating that HIF-1alpha mediates TUBB3 induction in hypoxia. To investigate this phenomenon, the 5' flanking region of human TUBB3 was cloned upstream GFP as a reporter. This region contained the promoter gene, but activity of the reporter was unaffected by hypoxia. Thus, we looked at the 3' flanking region and, at +168 nucleotides from the stop codon, an HIF-1alpha binding site was proven to be active in hypoxia, using a construct in which the site was cloned downstream GFP as reporter gene. Deletion of the site in the construct abolished GFP enhancement upon hypoxia. Chromatin immu...Continue Reading

References

Jan 1, 1986·Annals of the New York Academy of Sciences·S B HorwitzR Zeheb
Nov 22, 1994·Proceedings of the National Academy of Sciences of the United States of America·D PandaL Wilson
Nov 24, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M MonzóC Martín
Feb 24, 2001·Cancer Metastasis Reviews·G L Semenza
Dec 26, 2001·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Junji TsurutaniKazuhiko Nakagawa
Aug 9, 2003·Cell Motility and the Cytoskeleton·Malathi HariFernando Cabral
Jan 27, 2004·Journal of Molecular Biology·Tilman Sánchez-ElsnerFrancisco Rodriguez-Sanz
Jun 1, 2005·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A ParadisoV Lorusso
Aug 3, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Pascal SèveCharles Dumontet
Sep 13, 2005·Biochemical and Biophysical Research Communications·William G Kaelin
Sep 15, 2005·Experimental Physiology·Patrick H Maxwell
Nov 19, 2005·Cancer Biology & Therapy·Juan A Diaz-GonzalezLuis Montuenga
May 6, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gabriella FerrandinaCristiano Ferlini

❮ Previous
Next ❯

Citations

Mar 9, 2013·Cell Death & Disease·Y ZhaoM Tan
Feb 12, 2010·Nature Reviews. Cancer·Maria Kavallaris
Mar 1, 2012·The Journal of Biological Chemistry·Marisa CarbonaroParaskevi Giannakakou
Feb 12, 2013·BMC Cancer·Silvia PrisleiCristiano Ferlini
Aug 4, 2012·PloS One·Cinzia BaranelloCristiano Ferlini
Dec 25, 2012·Expert Review of Anticancer Therapy·Diana P EnglishAlessandro D Santin
Dec 18, 2013·Seminars in Pediatric Neurology·Christos D KatsetosPavel Dráber
May 23, 2012·Neurobiology of Aging·Chengyu ShengShengdi Chen
Sep 1, 2015·Critical Reviews in Oncology/hematology·E DiamondD M Nanus
May 26, 2009·Cell Motility and the Cytoskeleton·Jennifer Saussede-AimCharles Dumontet
Apr 27, 2011·Journal of Cellular Physiology·Marta De DonatoCristiano Ferlini
Jan 31, 2012·International Journal of Cancer. Journal International Du Cancer·Akiko HoriuchiIkuo Konishi
Aug 4, 2009·Journal of Cellular Physiology·Christos D KatsetosPavel Dráber
Oct 21, 2015·Analytical Cellular Pathology (Amsterdam)·Daniele FanaleViviana Bazan
Feb 6, 2013·Expert Opinion on Therapeutic Targets·Roshan KarkiCristiano Ferlini
Feb 17, 2015·Cancer Cell International·Elsa N Garza-TreviñoHerminia G Martínez-Rodríguez
May 16, 2015·Seminars in Pediatric Neurology·Christos D KatsetosPavel Dráber
Feb 11, 2015·Biochimica Et Biophysica Acta·Viswanath DasJohn H Miller
Sep 27, 2014·Drug Discovery Today·Qingyi MaLubo Zhang
Sep 12, 2012·Biochemical Pharmacology·Simona MozzettiCristiano Ferlini
Feb 20, 2015·Journal of the National Cancer Institute·Angela Broggini-TenzerMartin Pruschy
Jul 6, 2014·Frontiers in Oncology·Amelia L ParkerJoshua A McCarroll
Feb 1, 2013·Yonsei Medical Journal·Jun-Eul HwangIk-Joo Chung
May 28, 2014·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Kim M SmitsPhilippe Lambin
Aug 23, 2016·Molecular Informatics·Marco PersicoCaterina Fattorusso
Sep 22, 2016·Proceedings of the National Academy of Sciences of the United States of America·Chia-Ping Huang YangSusan Band Horwitz
Apr 4, 2017·Biochimica Et Biophysica Acta. General Subjects·Jiří ŘehulkaViswanath Das
Jul 6, 2017·International Journal of Molecular Sciences·Amelia L ParkerMaria Kavallaris
Apr 11, 2009·Virchows Archiv : an International Journal of Pathology·A PortyankoE Cherstvoy
Jan 8, 2014·Oncology Letters·Steven PowellMark Klein
Jul 15, 2015·The International Journal of Biological Markers·Ariel O ZwengerBernardo A Leone

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.