Bedeutung von Regulatoren des Zellzyklus bei Tumoren: Ein Überblick für Urologen

Zusammenfassung

Der Zellzyklus ist von fundamentaler Bedeutung für ein malignes Geschehen. Ein entsprechendes Verständnis dafür ist notwendig, wenn wir die Grundlagen von Krebs, sowie die spezifischen diagnostischen und therapeutischen Maßnahmen verstehen wollen.

Abstract

As the cell cycle is a fundamental component of malignancy, a proper understanding of it is necessary if we are to understand the basis of cancer, and its specific diagnostic and treatment measures.

Key words

Cell cycle - Tumors - p53 Protein - Cyclin

Literatur

• 1 Nurse P, Masui Y, Hartwell L. Understanding the cell cycle.  Nature Med. 1998;  4 1103-1111
• 2 Roberts J. Evolving ideas about cyclins.  Cell. 1999;  98 129-132
• 3 Lees J, Weinberg R A. Tossing monkey wrenches into the clock: New ways of treating cancer.  Proc Nat Acad Sci USA. 1999;  96 4221-4223
• 4 Leone G, DeGregori J, Jakoi L, Cook J, Nevins J. Collaborative role of E2F transcriptional activity and G₁ cyclin dependent kinase activity in the induction of S phase.  Proc Nat Acad Sci USA. 1999;  96 6626-6631
• 5 Hartwell L H. Twenty five years of cell cycle genetics.  Genetics. 1991;  129 975-980
• 6 Zachariae W, Nasmyth N. Whose end is destruction: cell division and the anaphase-promoting complex.  Genes and Development. 1999;  13 2039-2058
• 7 Mutoh M, Lung F, Long Y, Roller P, Sikorski R, O'Connor P. A p21 carboxyl-terminal peptide exhibited cyclin dependent kinase inhibitory activity and cytotoxicity when introduced into human cells.  Cancer Res. 1999;  59 3480-3488
• 8 Guis D, Ezhevsky S, Becker-Hapak M, Nagahara H, Wei M, Dowdy S. Transduced p16 peptides inhibit hypophosphorylation of the retinoblastoma protein and cell cycle progression prior to activation of CDK2 complexes late in G₁ .  Cancer Res. 1999;  59 2577-2580
• 9 Wang T C, Cardiff R D, Zuckerberg L, Lees E, Arnold A, Schmidt E V. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice.  Nature. 1994;  369 669-671
• 10 Nabori T, Miura K, Wu D, Lois A, Takabayashi K, Carson D. Deletions of the cyclin-dependent kinase and inhibitor gene in multiple human cancers.  Nature. 1994;  368 753-756
• 11 Jarrard D, Sarkar S, Shi V, Yeager T, Magrane G, Kinoshita H, Nassif N, Meisner L, Newton M, Waldman F, Reznikoff C. p16/pRb pathway alterations are required for bypassing senescence in human prostate epithelial cells.  Cancer Res. 1999;  59 2957-2964
• 12 Pomerantz J, Schreiber, Agus N, Liegeois N, Silverman A, Alland L, Chin L, Potes J, Chen K, Orlow I, Lee H W, Cordon-Cardo C, DePinho R. The INK4a tumor suppressor gene product, p19^arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53.  Cell. 1998;  92 713-723
• 13 Oliner J D, Kinzler K W, Meltzer P S, George D, Vogelstein B. Amplification of a gene encoding a p53 associated protein in human sarcomas.  Nature. 1992;  358 80-83
• 14 Zhang Y, Xiong Y, Yarborough W. ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 pathways.  Cell. 1998;  92 725-734
• 15 Fero M, Randel E, Gurley K, Roberts J, Kemp C. The murine gene p27Kip1 is haplo-insufficient for tumour suppression.  Nature. 1998;  396 177-180
• 16 Ponce-Castaneda M, Lee M H, Latres E, Polyak K, Lacombe L, Montgomery K, Mathew S, Krauter K, Scheinfeld J, Massague J, Cordon-Cardo C. p27Kip1: chromosome mapping to 12p12-12p13.1 and absence of mutations in human tumors.  Cancer Res. 1995;  55 1211-1214
• 17 Cote R, Shi Y, Groshen S, Feng A, Cordon-Cardo C, Skinner D, Lieskovosky G. Association of p27Kip1 levels with recurrence and survival in patients with stage C prostate carcinoma.  J Natl Canc Inst. 1998;  90 916-920
• 18 Schaefer D I, Livanos E M, White A E, Testy T D. Multiple mechanisms of N-(phosphonoacetyl)-L-aspartate drug resistance in SV40-infected precrisis human fibroblasts.  Cancer Res. 1993;  53 4946-4951
• 19 Kirn D, Hermiston T. Induction of an oncogenic fusion protein by a viral gene - a nwe chapter in an old story.  Nature Med. 1999;  5 991-992
• 20 Cordon-Cardo C, Zhang Z F, Dalbagni G, Drobniak M, Charytonowicz E, Hu S X, Zu H G, Reuter V, Benedict W E. Cooperative effects of p53 and Rb alterations in primary superficial bladder tumors.  Cancer Res. 1997;  57 1217-1221
• 21 Cross S M, Sanchez C A, Morgan C A, Schimke M K, Ramel S, Idzerda R L, Raskind W H, Reid B J. A p53-dependent mouse spindle checkpoint.  Science. 1995;  267 1353-1356
• 22 Chan T A, Hermeking H, Lengauer C, Kinzler K W, Vogelstein B. 14-3-30 is required to prevent mitotic catastrophe after DNA damage.  Nature. 1999;  401 616-620
• 23 Fukasawa K, Choi T, Kuriyama R, Rulong S, Vande Woude G F. Abnormal centrosome amplification in the absence of p53.  Science. 1996;  271 1744-1747
• 24 O'Connor P M, Ferris D K, Pagano M, Draetta G, Pines J, Hunter T, Longo D L, Kohn K W. G2 delay induced by nitrogen mustard in human cells affects cyclin A/CDK2 and cyclin B/CDC-2 kinase complexes differently.  J Biol Chem. 1993;  268 8298-8308
• 25 Komarov P, Lomarova E, Kandratov R, Christov-Tselkov K, Coon J, Chernov M, Gudkov A. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy.  Science. 1999;  258 1733-1737
• 26 Chen Y N, Sharma S K, Ramsey T M, Jiang L, Martin M, Baker K, Adams P, Bair K, Kaelin W. Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists.  Proc Natl Acad Sci. 1999;  96 4325-4329
• 27 Megyesi J, Price P, Tamayo E, Safirstein R. The lack of functional p21 gene ameliorates progression to chronic renal failure.  Proc Natl Acad Sci. 1999;  96 10830-10835
• 28 McMahen C, Suthiphongchai T, DiRenzo J, Ewen M. D/CAF associates with cyclin D₁ and potentiates its activation of the estrogen receptor.  Proc Natl Acad Sci. 1999;  96 5382-5387
• 29 Gonzalgo M, Hayashida T, Bender C, Pao M, Tsai Y, Gonzales F, Nguyen H, Nguyen T, Jones P. The role of DNA methylation in expression of the p19/p16 locus in human bladder cancer lives.  Cancer Res. 1998;  38 1245-1252
• 30 Jarrod D, Sarkar S, Shi Y, Yeager T, Magrave G, Kinoshita H, Nassif N, Meisner L, Newton M, Waldman F, Reznikoff C. p16/Rb pathway alterations are required for bypassing senescence in human prostate epithelial cells.  Cancer Res. 1999;  59 2957-2964
• 31 Chaubert P, Guillou L, Kurt A M, Bertholet M M, Metthez G, Leisinger H J, Bosman F, Shaw P. Frequent p16^INK4 (MST1) gene inactivation in testicular germ cell tumors.  Am J Path. 1997;  151 859-865
• 32 DelPizzo J, Borkowski A, Jacobs S, Kypriano N. Loss of cell cycle regulators p27^Kip1and cyclin E in transitional cell carcinoma of the bladder correlates with tumor grade and patient survival.  Am J Path. 1999;  155 1129-1135
• 33 Sgambato A, Migaldi M, Faraglia B, Garagnani L, Romano G, DeGaetani C, Ferrari P, Capelli G, Trentini G, Citadini A. Loss of p27^Kip1 expression correlates with tumor grade and with reduced disease free survival in primary superficial bladder cancers.  Cancer Res. 1999;  59 3245-3250
• 34 Tsihlias J, Kapusta L, DeBoer G, Morava-Protzner I, Zbieranowski I, Bhattacharya N, Catzavelos C, Klotz L, Slingerland J. Loss of cyclin dependent kinase inhibitor p27^Kip1 is a novel prognostic factor in localized human prostate adenocarcinoma.  Cancer Res. 1998;  52 542-548
• 35 Nakayama K, Ishida N, Shyrane M, Inomata H, Inoue T, Shishido N, Horr I, Loh D, Nakayama K. Mice lacking p27^Kip1 display increased body size, multiple organ hyperplasia, retinal dysplasia and pituitary tumors.  Cell. 1996;  85 707-720
• 36 Kawamata N, Morosetti R, Miller C W, Park D, Spirin K S, Nakamaki T, Takeuchi S, Hoffa Y, Koeffler H P. Molecular analysis of the cyclin dependent kinase inhibitor gene p27^Kip1 in human malignancies.  Cancer Res. 1995;  55 2266-2269