Consequences of p16 tumor suppressor gene inactivation in mycosis fungoides and Sézary syndrome and role of the bmi-1 and ras oncogenes in disease progression.
In examining the expression of oncogenes and tumor suppressor genes in mycosis fungoides and Sézary syndrome, we found the cell cycle-regulating protein p16 to be absent in T cells. Immunohistochemical staining with p16-specific antibodies showed that the number of p16-expressing cells in cutaneous lesions decreases in late stages. The repression of p16 was not attributable to deletion or methylation of this gene; however, the Bmi-1 oncogene, a known suppressor of p16, was present in mycosis fungoides and Sézary syndrome cell lines and skin lesions. The absence of p16 correlated with the phosphorylation of the retinoblastoma protein on cyclin D/CDK4- or cyclin D/CDK6-specific sites. Ki-ras, which stimulates phosphorylation of retinoblastoma via cyclin-dependent kinases, was found in all tested cutaneous T-cell lymphoma samples; and its expression generally was stronger in advanced stages. Thus, cutaneous T-cell lymphoma cells show changes in oncogene and tumor suppressor gene expression that increase proliferation.
Zhang
Chunlei
C
Department of Dermatology, University Hospital of Zurich, CH-8091 Zurich, Switzerland.
Toulev
Albena
A
Department of Dermatology, University Hospital of Zurich, CH-8091 Zurich, Switzerland.
Kamarashev
Jivko
J
Department of Dermatology, University Hospital of Zurich, CH-8091 Zurich, Switzerland.
Qin
Jian-Zhong
JZ
Department of Dermatology, University Hospital of Zurich, CH-8091 Zurich, Switzerland.
Dummer
Reinhard
R
Department of Dermatology, University Hospital of Zurich, CH-8091 Zurich, Switzerland.
Döbbeling
Udo
U
Department of Dermatology, University Hospital of Zurich, CH-8091 Zurich, Switzerland. Electronic address: Udo.Doebbeling@usz.ch.
D049109:Cell Proliferation; D018450:Disease Progression; D019942:Genes, p16; D011905:Genes, ras; D006801:Humans; D009182:Mycosis Fungoides / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010766:Phosphorylation; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000378:metabolism; D012751:Sezary Syndrome / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured
C069077:BMI1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D063150:Polycomb Repressive Complex 1