Hypoxia regulation of the cell cycle in malignant melanoma: putative role for the cyclin-dependent kinase inhibitor p27

Journal of Cutaneous Pathology
Michael MurphyMassimo Loda

Abstract

Intratumor hypoxia has been shown to promote more aggressive and metastatic cancer phenotypes that are associated with treatment resistance and poor prognosis. Cellular proliferation and its control are known to be important components of tumor progression. Hypoxia induces cell-cycle arrest in cultured cell lines, possibly via up-regulation of the cyclin-dependent kinase inhibitor p27. The effect of hypoxia on cell-cycle regulation in excised human tumors has not been investigated. We performed immunohistochemistry for p27 and Ki-67 on 10 formalin-fixed paraffin-embedded metastatic melanomas, selected on the basis of histological evidence of zonal/geographic necrosis, adjacent to areas with viable perivascular tumor cells. In the majority of cases, there was a significant increase in p27 staining in cells adjacent to necrotic areas compared to perivascular zones. An inverse staining pattern between Ki-67 and p27 was identified in these tumors. Tumors with no zonal increase in p27 staining demonstrated a diffuse pattern of staining for Ki-67 within tumor nests. While increased cellular proliferation is a characteristic of cancer, subsets of human melanomas may retain the ability to regulate their rate of proliferation in respons...Continue Reading

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Citations

Jul 5, 2007·Journal of Mathematical Biology·Kieran SmallboneJ Michael Brady
Dec 25, 2004·The American Journal of Dermatopathology·Michael J KlukMichael Murphy
Nov 19, 2005·Journal of Cutaneous Pathology·J Andrew CarlsonMichael Murphy
Apr 7, 2005·Journal of Cutaneous Pathology·Thierry Simonart, Michel Heenen
Dec 10, 2014·Medical Oncology·Chun-Xiong ZhaoXiao-Hou Wu
Oct 20, 2004·Journal of Cutaneous Pathology·Qing LiJ Andrew Carlson
Sep 22, 2012·International Journal of Dermatology·Michael MurphyK Claffey
Aug 11, 2011·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Guangdi ChenGang Li
Dec 20, 2008·Clinics in Dermatology·J Andrew CarlsonAndrze J Slominski

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