Repeated exposure of epithelial cells to apoptotic cells induces the specific selection of an adaptive phenotype: Implications for tumorigenesis

The Journal of Biological Chemistry
Lanfei FengJerrold S Levine

Abstract

The consequences of apoptosis extend beyond the mere death of the cell. We have shown that receptor-mediated recognition of apoptotic target cells by viable kidney proximal tubular epithelial cells (PTECs) inhibits PTEC proliferation, growth, and survival. Here, we tested the hypothesis that continual exposure to apoptotic targets can induce a phenotypic change in responding PTECs, as in other instances of natural selection. In particular, we demonstrate that repeated exposure to apoptotic targets leads to emergence of a PTEC line (denoted BU.MPTSEL) resistant to apoptotic target-induced death. Resistance is exquisitely specific. Not only are BU.MPTSEL responders fully resistant to apoptotic target-induced death (∼85% survival versus <10% survival of nonselected cells) but do so while retaining sensitivity to all other target-induced responses, including inhibition of proliferation and growth. Moreover, the resistance of BU.MPTSEL responders is specific to target-induced apoptosis, as apoptosis in response to other suicidal stimuli occurs normally. Comparison of the signaling events induced by apoptotic target exposure in selected versus nonselected responders indicated that the acquired resistance of BU.MPTSEL cells lies in a ...Continue Reading

References

Jun 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·P S JatD Kioussis
Dec 6, 1997·Nature·R E VollI Girkontaite
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Nov 14, 2000·The Journal of Biological Chemistry·V StokaG S Salvesen
May 18, 2001·Nature·G I Evan, K H Vousden
Jun 19, 2001·The Journal of Biological Chemistry·M ChenR A Gottlieb
Dec 14, 2001·The Journal of Biological Chemistry·Muniswamy MadeshGyörgy Hajnóczky
Mar 26, 2003·Cell Death and Differentiation·I LavrikS Kirchhoff
May 23, 2003·Journal of the American Society of Nephrology : JASN·Joseph V Bonventre
Jan 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marija Cvetanovic, David S Ucker
Apr 23, 2005·Cancer Biology & Therapy·Anja KnottWolfgang Hillen
Dec 17, 2005·Cancer Research·Zhang WeihuaIsaiah J Fidler
Feb 24, 2006·Molecular Biology of the Cell·Christine BonzonDonald D Newmeyer
Apr 22, 2006·Cell Death and Differentiation·D V KryskoP Vandenabeele
May 19, 2006·The Journal of Biological Chemistry·Marija CvetanovicDavid S Ucker
Dec 26, 2006·Nature Medicine·Michel ObeidGuido Kroemer
Apr 23, 2008·Molecular and Cellular Biology·John-Paul UptonScott A Oakes
May 3, 2008·Cell Death and Differentiation·R B Birge, D S Ucker
May 8, 2008·Histochemistry and Cell Biology·Roland MollLutz Langbein
Jul 17, 2008·Nature Reviews. Molecular Cell Biology·Matthias Schäfer, Sabine Werner
Nov 27, 2008·The Journal of Clinical Investigation·Irini BournazouChristopher D Gregory
Jul 31, 2009·Oncogene·L P BillenD W Andrews
Nov 17, 2009·The Journal of Biological Chemistry·Vimal A PatelJerrold S Levine
Dec 2, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lars EsmannTamás Laskay
Feb 11, 2010·Current Opinion in Immunology·Alberto Mantovani, Antonio Sica
Feb 17, 2010·Apoptosis : an International Journal on Programmed Cell Death·Christoph PeterKirsten Lauber
Mar 23, 2010·Cell·Laurence ZitvogelGuido Kroemer
Jul 16, 2010·Developmental Cell·Mikala EgebladZena Werb
Oct 28, 2010·Science Signaling·Andreas Bergmann, Hermann Steller
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Mar 25, 2011·Kidney International·Jonathan M GallSteven C Borkan
Apr 5, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ivonne NaumannSimone Fulda
May 13, 2011·Journal of Leukocyte Biology·Andrew Devitt, Lindsay J Marshall

❮ Previous
Next ❯

Citations

Nov 1, 2018·Journal of Cellular Physiology·Masoud NajafiKeywan Mortezaee

❮ Previous
Next ❯

Related Concepts

Related Feeds

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

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.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.