Perlecan, a candidate gene for the CAPB locus, regulates prostate cancer cell growth via the Sonic Hedgehog pathway

Molecular Cancer
Milton W DattaSumana Datta

Abstract

Genetic studies associated the CAPB locus with familial risk of brain and prostate cancers. We have identified HSPG2 (Perlecan) as a candidate gene for CAPB. Previously we have linked Perlecan to Hedgehog signaling in Drosophila. More recently, we have demonstrated the importance of Hedgehog signaling in humans for advanced prostate cancer. Here we demonstrate Perlecan expression in prostate cancer, and its function in prostate cancer cell growth through interaction and modulation of Sonic Hedgehog (SHH) signaling. Perlecan expression in prostate cancer tissues correlates with a high Gleason score and rapid cell proliferation. Perlecan is highly expressed in prostate cancer cell lines, including androgen insensitive cell lines and cell lines selected for metastatic properties. Inhibition of Perlecan expression in these cell lines decreases cell growth. Simultaneous blockade of Perlecan expression and androgen signaling in the androgen-sensitive cell line LNCaP was additive, indicating the independence of these two pathways. Perlecan expression correlates with SHH in tumor tissue microarrays and increased tumor cell proliferation based on Ki-67 immunohistochemistry. Inhibition of Perlecan expression by siRNA in prostate cancer c...Continue Reading

References

May 1, 1994·International Journal of Cancer. Journal International Du Cancer·H C WuL W Chung
Jun 20, 1997·International Journal of Cancer. Journal International Du Cancer·K NackaertsG David
Oct 28, 1998·The Journal of Clinical Investigation·B SharmaR V Iozzo
Mar 3, 1999·American Journal of Human Genetics·M GibbsE A Ostrander
May 13, 2003·International Journal of Cancer. Journal International Du Cancer·Erin M ConlonEllen M Wijsman
Sep 17, 2003·Glycoconjugate Journal·John HassellEri Arikawa-Hirasawa
Nov 6, 2003·The Prostate·Douglas F EastonUNKNOWN International Consortium for Prostate Cancer Genetics
Nov 6, 2003·The Prostate·Marta JanerGail P Jarvik
Dec 18, 2003·Bone·Geertje van der HorstMarcel Karperien
Sep 14, 2004·Nature·Sunil S KarhadkarPhilip A Beachy
Oct 16, 2004·Molecular Cancer·Tao ShengJingwu Xie

❮ Previous
Next ❯

Citations

Dec 11, 2008·Urological Research·Metin OnaranIbrahim Bozkirli
Jun 12, 2013·PloS One·Stephanie L SwiftLindsay J Georgopoulos
Oct 23, 2013·Angiogenesis·Xander M R van Wijk, Toin H van Kuppevelt
Jan 27, 2009·Molecular Membrane Biology·Shu-Chun Chang, Anthony I Magee
Apr 23, 2008·The Journal of Cell Biology·Jason J ZoellerRenato V Iozzo
Jul 17, 2015·Connective Tissue Research·Stephen DouglassRenato V Iozzo
Nov 19, 2015·Frontiers in Oncology·Angela ChoEmily K Colvin
May 22, 2013·ISRN Oncology·Anastasia V SuhovskihElvira V Grigorieva
Apr 20, 2016·Nature Reviews. Urology·Jennifer MunkleyDavid J Elliott
Feb 27, 2008·Microscopy Research and Technique·Gregory Bix, Renato V Iozzo
Jul 18, 2008·Clinical Proteomics·Raghothama ChaerkadyAkhilesh Pandey
Jul 17, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Kathryn D RodgersOlena Jacenko
Mar 22, 2019·International Journal of Molecular Sciences·Emma Scott, Jennifer Munkley
Mar 26, 2019·The FEBS Journal·Achilleas D TheocharisNikos K Karamanos
Jan 11, 2007·Human Molecular Genetics·Kathryn D RodgersOlena Jacenko
Feb 22, 2012·Nature Reviews. Urology·Iris J Edwards
Jan 4, 2013·The FEBS Journal·Anna WadeJoanna J Phillips
Jul 11, 2019·American Journal of Respiratory and Critical Care Medicine·David B Frank, Edward E Morrisey
Dec 16, 2010·Journal of Cellular and Molecular Medicine·Renato V Iozzo, Ralph D Sanderson
Nov 20, 2012·Proteomics. Clinical Applications·Arivusudar MarimuthuAkhilesh Pandey
May 2, 2020·Biomolecules·Marley J BinderAlister C Ward
Mar 4, 2020·Journal of Mammary Gland Biology and Neoplasia·Malin JanssonMalin Sund
Feb 11, 2011·Birth Defects Research. Part A, Clinical and Molecular Teratology·Chengjin ZhangGregory J Cole
Nov 21, 2007·The Journal of Biological Chemistry·Benjamin P WoodallRenato V Iozzo
Sep 19, 2020·The International Journal of Biochemistry & Cell Biology·James Melrose
May 30, 2013·Journal of Proteome Research·He-chun LinMing Yao
May 9, 2009·Matrix Biology : Journal of the International Society for Matrix Biology·Jason J ZoellerRenato V Iozzo

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
PCR
dot blot
transfections
transfection
Immunoprecipitation
pulls down
co-immunoprecipitation
Co-IP

Software Mentioned

LocusLink
Primer Express

Related Concepts

Related Feeds

Cancer Stem Cells in Glioblastoma

Glioblastoma is the most common and aggressive type of brain tumor. It contains a population of tumor initiating stem cell-like cells known as cancer stem cells. Investigations are ongoing into these cancer stem cells found in these solid tumors which are highly resistance to treatment. Here is the latest research on cancer stem cells in glioblastoma.