Open AccessTelomere dysfunction and inactivation of the p16 INK4a /Rb pathway in pyothorax‐associated lymphoma
Author(s) -
Tresnasari Kristianti,
Takakuwa Tetsuya,
Ham Maria Francisca,
Rahadiani Nur,
Nakajima Hiroo,
Aozasa Katsuyuki
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00482.x
Subject(s) - telomere , telomerase , genome instability , biology , cell culture , lymphoma , cancer research , chromosome instability , cell division , cell cycle , microbiology and biotechnology , cell , genetics , gene , dna , dna damage , immunology , chromosome
Previous studies have indicated that genome instability is involved in the lymphomagenesis of pyothorax‐associated lymphoma (PAL), which develops in patients with a long‐standing history of pyothorax. One of the well‐known causes of genome instability is telomere dysfunction. In the present study, the condition of telomeres was analyzed in the cell lines and clinical samples from PAL. Telomere length (TL) in PAL cell lines was extremely short (<4.5 kbp). TL in tumor samples was broad in range, and shorter than that in the peripheral blood leukocytes from the matched patients. Three of five PAL cell lines showed frequent loss of telomere signals (telomere erosion); however, telomerase activity in PAL cell lines was similar to that in Burkitt lymphoma cell lines. Rb expression was detected in three PAL cell lines and four of 15 clinical samples, respectively. Rb protein expressed in three PAL cell lines was heavily phosphorylated, indicating that function of Rb protein was suppressed. p16 INK4a expression was not detected in either cell lines or clinical samples. The promoter region in p16 INK4a was heavily methylated in all cell lines as well as the clinical samples. Inactivation of the p16 INK4a /Rb pathway may allow continuous cell division and critical telomere shortening, which induce genome instability, finally leading to malignant transformation. Taken together, telomere dysfunction and inactivation of the p16 INK4a /Rb pathway might play a role for PAL development. ( Cancer Sci 2007; 98: 978–984)