Regulation of the G1/S phase of the cell cycle and alterations in the RB pathway in human lung cancer

Expert Review of Anticancer Therapy
Harriet Wikman, Eeva Kettunen

Abstract

The retinoblastoma (RB)-Cyclin (CCN)D1-p16 cell cycle pathway has a crucial role in lung tumorigenesis. Impairment of the RB pathway has been shown to occur in almost all lung tumors. A deregulation at any level of this core RB pathway seems to make cells insensitive to the mitogenic signaling that is required for cell cycle progression. To date, almost all participants in this pathway have been shown to be altered to a various degree in lung tumors. Some of the alterations are mutually exclusive, including RB and p16INK4A . In small cell lung cancer, the RB tumor suppressor gene is inactivated in almost 90% of the tumors, whereas in non-small cell lung cancer, the cyclin-dependent kinase (CDK)4 inhibitor p16INK4A is inactivated in 40-60% of the tumors. Many mechanisms may be responsible for activating the RB-Cyclin D1 pathway, including activating (CDK4) and inactivating mutations (p16INK4A ), deletions (RB and p16INK4A ), amplifications (CCND1 and CDK4), silencing methylation (p16INK4A and RB), and hyper-phosphorylation (RB). As some of these alterations, such as p16INK4A methylation, can also be detected in bronchial lavage and serum, they could potentially serve as useful markers for the early detection of lung cancer. This...Continue Reading

References

Apr 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J M HorowitzR A Weinberg
Apr 1, 1971·Proceedings of the National Academy of Sciences of the United States of America·A G Knudson
May 17, 1995·Journal of the National Cancer Institute·M J KelleyB E Johnson
Sep 15, 1994·International Journal of Cancer. Journal International Du Cancer·V GouyerC Brambilla
Aug 2, 1994·Proceedings of the National Academy of Sciences of the United States of America·I E SchauerR A Sclafani
Mar 1, 1994·Molecular and Cellular Biology·M Meyerson, E Harlow
Feb 8, 1996·International Journal of Cancer. Journal International Du Cancer·M SakaguchiH Matsuda
Mar 15, 1996·International Journal of Cancer. Journal International Du Cancer·M R RusinC C Harris
Jun 1, 1996·Virchows Archiv : an International Journal of Pathology·H UsudaM Naito
Jun 24, 1997·Proceedings of the National Academy of Sciences of the United States of America·K HelinP Norgaard
Jan 1, 1997·British Journal of Cancer·D C BetticherP S Hasleton
Nov 14, 1997·International Journal of Cancer. Journal International Du Cancer·D C BetticherJ Heighway
Feb 14, 1998·International Journal of Cancer. Journal International Du Cancer·A MarchettiG Bevilacqua
Feb 26, 1998·American Journal of Respiratory Cell and Molecular Biology·V GouyerE Brambilla
May 16, 1998·International Journal of Cancer. Journal International Du Cancer·H TanakaH Matsuda
Jun 13, 1998·Molecular Pathology : MP·R Donnellan, R Chetty
Jun 30, 1998·International Journal of Cancer. Journal International Du Cancer·K KashiwabaraT Nakajima
Jun 30, 1998·International Journal of Cancer. Journal International Du Cancer·M VolmW Rittgen
Sep 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·S A BelinskyJ G Herman
Mar 2, 1999·Journal of the National Cancer Institute·S A AhrendtD Sidransky
Jun 25, 1999·Cell·Y GengP Sicinski
Sep 22, 1999·Molecular and Cellular Biology·T TsutsuiH Kiyokawa
Nov 5, 1999·The Journal of Pathology·J YuanK Strebhardt
Dec 2, 1999·Genes & Development·M SugimotoE Hara
Feb 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·H HermekingK W Kinzler
May 2, 2000·Current Pharmaceutical Design·J K Buolamwini
Sep 14, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M KerstingM Schuermann

❮ Previous
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Citations

Jan 12, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Michalis V KaramouzisAthanasios G Papavassiliou
Sep 11, 2012·Nature·UNKNOWN Cancer Genome Atlas Research Network
Feb 20, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gerhard HamiltonTheresia Thalhammer
Jul 29, 2008·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Kristell BastideSylvie Chevillard
Sep 13, 2006·Cancer Genetics and Cytogenetics·Marina MustiSakari Knuutila
Sep 2, 2016·BioFactors·Marta PiroddiFrancesco Galli
Feb 23, 2017·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·J Z WangS J Shen
Jul 30, 2014·International Journal of Molecular Medicine·Miho SuzukiYasuko Kitagishi
Jan 30, 2020·Journal of Physiology and Biochemistry·Yien XiangXuewen Zhang
Jun 9, 2007·The Journal of Biological Chemistry·Seetha V SrinivasanErik S Knudsen
Feb 23, 2007·Molecular Cancer Research : MCR·Michalis V KaramouzisAthanasios G Papavassiliou
Nov 24, 2006·Molecular Cancer Therapeutics·Barbara VischioniGiuseppe Giaccone
Oct 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wei WangXifeng Wu

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