Breast tumor kinase/protein tyrosine kinase 6 (Brk/PTK6) activity in normal and neoplastic biliary epithelia

Journal of Hepatology
Yoshiaki MizuguchiAnthony J Demetris

Abstract

Breast tumor kinase (BRK) augments proliferation and promotes cell survival in breast cancers via interactions with SH2 and SH3 ligand-containing proteins, such as receptor tyrosine kinases (RTK; e.g. EGFR, ErbB2/neu). Since RTK contribute to cholangiocarcinoma (CC) evolution we probed BRK protein expression and function in normal and CC livers. Immunohistochemical staining of normal livers and CC (n=93) in a tissue microarray and three CC and an immortalized human cholangiocyte cell lines (real-time PCR, Western blotting, siRNA) were used to study the functional relationships between BRK, EGFR, ErbB2, SAM68, and SPRR2a. BRK protein was expressed in normal human intrahepatic bile ducts; all CC cell lines and a majority of CC showed strong BRK protein expression. Multiplex immunostaining/tissue cytometry and immunoprecipitation studies showed: 1) BRK co-localized with EGFR and ErbB2/neu; 2) BRK(high)/EGFR(high)-co-expressing CC cells had significantly higher Ki67 labeling and; 3) stronger BRK protein expression was seen in perihilar and distal CC than intrahepatic CC and directly correlated with CC differentiation. In cell lines, BRK expression augmented proliferation in response to exogenous EGF, whereas BRK siRNA significantly...Continue Reading

References

Apr 28, 1994·Nature·S FumagalliS A Courtneidge
Jul 27, 2000·Molecular and Cellular Biology·J J DerryA L Tyner
Feb 15, 2001·Mammalian Genome : Official Journal of the International Mammalian Genome Society·X LiD J Baylink
Jul 18, 2002·The Journal of Biological Chemistry·Haoqun Qiu, W Todd Miller
Mar 17, 2004·Archives of Otolaryngology--head & Neck Surgery·Ho-Sheng LinZijie Sun
Apr 13, 2004·Anti-cancer Drugs·Amanda J Harvey, Mark R Crompton
Jun 12, 2004·Seminars in Liver Disease·Yasser Shaib, Hashem B El-Serag
Feb 4, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Alphonse E Sirica
Jun 1, 2005·Biochimica Et Biophysica Acta·Tong Wu
Sep 24, 2005·The Journal of Biological Chemistry·Kiven Erique LukongStéphane Richard
May 3, 2006·The American Journal of Pathology·Monika KasprzyckaMariusz A Wasik
Jul 21, 2006·Cancer Biology & Therapy·Rosemarie E SchmandtDavid M Gershenson
Aug 15, 2006·Trends in Cell Biology·Pankaj K Singh, Michael A Hollingsworth
Nov 14, 2006·Bioorganic & Medicinal Chemistry·Fatih M UckunKatayoon H Emami
Jul 17, 2008·Nature Reviews. Molecular Cell Biology·Matthias Schäfer, Sabine Werner
Aug 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Bin XiangSenthil K Muthuswamy
Aug 8, 2009·The American Journal of Pathology·Amanda J HarveyMark R Crompton
Mar 3, 2010·Biochimica Et Biophysica Acta·Patrick M Brauer, Angela L Tyner
Mar 9, 2010·Cellular Signalling·J Michael Bradshaw
Apr 22, 2010·Cancer Research·Alexander M Xu, Paul H Huang
Jul 7, 2010·Cell·Mark A Lemmon, Joseph Schlessinger
Sep 14, 2010·Current Opinion in Pharmacology·Julie H OstranderCarol A Lange
Nov 15, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kumiko IsseAnthony J Demetris
Jun 4, 2013·Clinical & Experimental Metastasis·Susan SpechtAnthony J Demetris
Oct 15, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yoshiaki MizuguchiAnthony J Demetris

❮ Previous
Next ❯

Citations

Nov 1, 2015·Journal of Alzheimer's Disease : JAD·Andrea F N RosenbergerSaskia M van der Vies
Feb 16, 2019·Transplantation·Michelle A Wood-TrageserAnthony J Demetris
Jul 28, 2020·Journal of Clinical Medicine·Wook Jin
Aug 24, 2017·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Anthony J Demetris
Sep 24, 2021·Journal of Experimental & Clinical Cancer Research : CR·Chaoqun LiuLiang Zhao

❮ Previous
Next ❯

Related Concepts

Related Feeds

Breast Invasive Carcinoma

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Carcinoma, Ductal

Ductal carcinoma is a malignant neoplasm involving the ductal systems of any of a number of organs, such as the mammary glands, pancreas, prostate or lacrimal gland. Discover the latest research on ductal carcinoma here.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.

Breast Invasive Carcinoma (Keystone)

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

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.