Functional identification of a BAC clone from 16q24 carrying a senescence gene SEN16 for breast cancer cells.
We have identified an 85 kb BAC clone, 346J21, that carries a cell senescence gene (SEN16), previously mapped to 16q24.3. Transfer and retention of 346J21 in breast cancer cell lines leads to growth arrest after 8-10 cell doublings, accompanied by the appearance of characteristic senescent cell morphology and senescence-associated acid beta-galactosidase activity. Loss of transferred BAC results in reversion to the immortal growth phenotype of the parental cancer cell lines. BAC 346J21 restores senescence in the human breast cancer cell lines, MCF.7 and MDA-MB468, and the rat mammary tumor cell line LA7, but not in the human glioblastoma cell line T98G. We postulate that inactivation of both copies of SEN16 is required for the immortalization of breast epithelial cells at an early stage of tumorigenesis. Positional mapping of 346J21 shows that SEN16 is distinct from other candidate tumor suppressor genes reported at 16q24.
Kaur
Gursurinder Pal
GP
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA. pkaur001@temple.edu
Reddy
Deepthi E
DE
Zimonjic
Drazen B
DB
de Riel
Jon K
JK
Athwal
Raghbir S
RS
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D022202:Chromosomes, Artificial, Bacterial; D002885:Chromosomes, Human, Pair 16; D005260:Female; D018014:Gene Transfer Techniques; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins