Cellular senescence of a human bladder carcinoma cell line (JTC-32) induced by a normal chromosome 11.
Human chromosome 11 is expected to carry tumor suppressor genes for a variety of human cancers, including bladder carcinoma. To examine the functional role of a putative tumor suppressor gene(s) on this chromosome in the development of bladder carcinoma, we performed microcell-mediated transfer of chromosome 11 into the bladder carcinoma cell line, JTC-32. Fifteen of 20 colonies formed by the transfer experiment showed a remarkable change in cell morphology. They flattened and ceased growing, or senesced, prior to 10 population doublings. The presence of transferred chromosome 11-derived fragments in the growth-arrested cells was confirmed by PCR-based polymorphism analyses. The remaining 5 microcell hybrid clones exhibited a parental cell-like morphology, and presumably escaped from senescence, which was accompanied by deletions and/or rearrangements of the transferred chromosome 11. On the other hand, a transferred normal chromosome 7 neither changed the cell morphology nor arrested the cell growth. These results support the hypothesis that chromosome 11 contains a gene or genes which restore the senescence program lost during the immortalization process of JTC-32 cells.
Kugoh
H
H
Department of Molecular and Cell Genetics, School of Life Sciences, Faculty of Medicine, Tottori University, Yonago, Japan.
Fujiwara
M
M
Kihara
K
K
Fukui
I
I
Horikawa
I
I
Schulz
T C
TC
Oshimura
M
M
D000368:Aged; D016922:Cellular Senescence / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*