Brk is coamplified with ErbB2 to promote proliferation in breast cancer.

Proceedings of the National Academy of Sciences of the United States of America
Bin XiangSenthil K Muthuswamy

Abstract

Amplification of the receptor tyrosine kinase ErbB2 is frequently observed in breast cancer. Amplification of erbB2 is also associated with multiple genomic gains and losses; however, the importance of these associated changes is largely unknown. We demonstrate that Brk, a cytoplasmic tyrosine kinase, is coamplified and coexpressed with ErbB2 in human breast cancers. ErbB2 interacts with Brk and increases its intrinsic kinase activity. Expression of Brk enhances the ErbB2-induced activation of Ras/MAPK signaling and cyclin E/cdk2 activity to induce cell proliferation of mammary 3-dimensional acini in culture. In a murine model of breast cancer, expression of Brk was found to shorten the latency of ErbB2-induced tumors by promoting cell proliferation, with no effect on protection from apoptosis. Furthermore, overexpression of Brk conferred resistance to the ability of Lapatinib, an ErbB2 kinase inhibitor, to inhibit ErbB2-induced proliferation. Thus, we identified Brk as a drug target for ErbB2-positive cancers.

References

Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·C T GuyW J Muller
Jun 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·K G DanielsonD Medina
Jul 18, 2002·The Journal of Biological Chemistry·Haoqun Qiu, W Todd Miller
Nov 15, 2002·The New England Journal of Medicine·Khandan KeyomarsiSarah S Bacus
Feb 4, 2003·Nature Medicine·Khandan KeyomarsiIsabelle Bedrosian
May 3, 2003·Oncology Research·Michael S Serfas, Angela L Tyner
Jun 12, 2003·Methods : a Companion to Methods in Enzymology·Jayanta DebnathJoan S Brugge
Apr 13, 2004·Anti-cancer Drugs·Amanda J Harvey, Mark R Crompton
May 3, 2005·Nature Reviews. Cancer·Nancy E Hynes, Heidi A Lane
May 5, 2005·Oncogene·Haoqun QiuW Todd Miller
Jul 27, 2005·Seminars in Cancer Biology·Kelly K Hunt, Khandan Keyomarsi
Feb 14, 2006·Methods in Enzymology·Bin Xiang, Senthil K Muthuswamy
Apr 11, 2006·Trends in Biochemical Sciences·Leon O Murphy, John Blenis
Jul 11, 2006·Nature Reviews. Molecular Cell Biology·Ami Citri, Yosef Yarden
Jul 25, 2006·Current Biology : CB·Andrew D Sharrocks

❮ Previous
Next ❯

Citations

Nov 30, 2011·Hormones & Cancer·Alessia LocatelliCarol A Lange
May 24, 2011·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Chuifeng FanEnhua Wang
Jun 18, 2010·The Journal of Biological Chemistry·Shin-Ae KangSeung-Taek Lee
May 2, 2012·The Journal of Biological Chemistry·Yiwei GaoNancy C Reich
Jul 16, 2010·Molecular & Cellular Proteomics : MCP·Bernard A LiuPiers D Nash
Apr 24, 2013·Molecular and Cellular Biology·Lingtao JinSumin Kang
Jul 30, 2010·PloS One·Hanna Y IrieJoan S Brugge
Jun 10, 2010·Future Oncology·Kai-Keen ShiuJorge S Reis-Filho
Mar 3, 2010·Biochimica Et Biophysica Acta·Patrick M Brauer, Angela L Tyner
Aug 16, 2015·Cancer Treatment Reviews·Valentina D'AmatoRoberto Bianco
Feb 18, 2010·International Journal of Cancer. Journal International Du Cancer·Edward Chan, Anjaruwee S Nimnual
Aug 8, 2009·The American Journal of Pathology·Amanda J HarveyMark R Crompton
Apr 14, 2016·Cancer Metastasis Reviews·Raghuveera Kumar Goel, Kiven Erique Lukong
May 23, 2015·Biochimica Et Biophysica Acta·Raghuveera Kumar Goel, Kiven Erique Lukong
Jun 19, 2015·Breast Cancer Research : BCR·Sun Hee ParkHanna Y Irie
Mar 17, 2015·Journal of Hepatology·Yoshiaki MizuguchiAnthony J Demetris
Aug 3, 2016·Biochemical and Biophysical Research Communications·Manish Kumar ThakurRamachandraiah Gosu
Oct 12, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Huiping ShiMin Jiang
Feb 19, 2017·Journal of Cellular Biochemistry·Won-Sik ShinSeung-Taek Lee
Jul 12, 2019·The Oncologist·Janakiraman SubramanianRama Krishna Kancha

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis