Selective loss of the transforming growth factor-beta apoptotic signaling pathway in mutant NRP-154 rat prostatic epithelial cells.
Retroviral insertional mutagenesis was used to select mutant NRP-154 rat prostate carcinoma cells resistant to transforming growth factor (TGF)-beta-induced cell death. Similar to the parental cells, a mutant clone, M-NRP1, expressed TGF-beta receptors and was still responsive to induction both of direct target genes by TGF-beta and of apoptosis by staurosporine or okadaic acid. In contrast, indicators of cell growth, strongly suppressed by TGF-beta in the parental cells, were unaffected in M-NRP1 cells. M-NRP1 cells overexpress the antiapoptotic protein, Bcl-xL, and show dysregulated expression and localization of a protein related to a novel human septin, ARTS (designation of apoptotic response to TGF-beta signals), cloned by homology to an exonic sequence flanked by the viral long terminal repeats in M-NRP1 cells and shown to make cells competent to undergo apoptosis in response to TGF-beta. We propose that ARTS might operate within the same apoptotic pathway as Bcl-xL and that M-NRP1 cells could serve as a useful model for characterization of this pathway.
Larisch-Bloch
S
S
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055, USA.
Danielpour
D
D
Roche
N S
NS
Lotan
R
R
Hsing
A Y
AY
Kerner
H
H
Hajouj
T
T
Lechleider
R J
RJ
Roberts
A B
AB
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008297:Male; D016254:Mutagenesis, Insertional; D019319:Okadaic Acid / Q000494:pharmacology; D011467:Prostate; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
C494813:Bcl2l1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D051020:bcl-X Protein; D019319:Okadaic Acid; D019311:Staurosporine