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Expression of P27 KIP1 is prognostic and independent of MYCN amplification in human neuroblastoma
Author(s) -
Bergmann Eckhard,
Wanzel Michael,
Weber Axel,
Shin Inhee,
Christiansen Holger,
Eilers Martin
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20010520)95:3<176::aid-ijc1030>3.0.co;2-z
Subject(s) - neuroblastoma , biology , gene duplication , cancer research , oncology , pathology , medicine , genetics , gene , cell culture
Amplification of the MYCN gene is significantly associated with an unfavorable prognosis and rapid progression in human neuroblastoma tumors. One potential mechanism by which MYCN may cause these effects is by deregulating cell proliferation. Tissue culture experiments support a model in which MYC genes stimulate cell cycle progression by antagonizing the function of the cell cycle inhibitor p27 kip1 . In culture, activation of MYC induces both sequestration of p27 kip1 by cyclin D complexes and its subsequent proteolytic degradation. We have tested whether this model applies to human neuroblastoma in a retrospective study of 100 primary tumor biopsy samples from neuroblastoma patients with a documented follow‐up. Consistent with this hypothesis, MYCN ‐amplified tumors express high levels of both cyclin A and proliferating cell nuclear antigen, 2 marker proteins of cell proliferation. Further, expression levels of p27 kip1 are of prognostic significance in human neuroblastoma patients. Similar to tissue culture systems, p27 kip1 is sequestered by cyclin D complexes in a subset of human neuroblastoma samples. Surprisingly, however, expression levels of p27 kip1 are prognostic independent of MYCN amplification, and tumors that have an amplified MYCN gene do not express elevated levels of D‐type cyclins or contain significantly lower levels of p27 kip1 . Our data do not support a model in which regulation of p27 kip1 function is an important mechanism by which amplified MYCN deregulates cell proliferation in neuroblastoma. © 2001 Wiley‐Liss, Inc.