Altered regulation of protein disulfide isomerase in cells resistant to the growth-inhibitory effects of transforming growth factor beta 1.
A murine keratinocyte cell line that is resistant to the growth-inhibitory effects of transforming growth factor beta 1 (TGF beta 1) was examined for differential gene expression patterns that may be related to the mechanism of the loss of TGF beta 1 responsiveness. Cells that were resistant to the growth-inhibitory effects of TGF beta 1 (KCR cells) were derived from K-ras-transformed BALB/MK keratinocytes (KC cells). Using a subtractive hybridization procedure with KC and KCR mRNAs, we isolated a complementary DNA clone for murine protein disulfide isomerase (PDI). The mRNA for PDI is inhibited by TGF beta 1 treatment in the parental KC cells, but not in the TGF beta 1-resistant KCR cells. Similar PDI down-regulation also occurs in other TGF beta-sensitive cells, but not in a human pancreatic carcinoma cell line which is insensitive to the growth-inhibitory effects of TGF beta 1. The results suggest that misregulation of PDI, an important component of co- and posttranslational modification systems, may be involved in the mechanism by which some cells escape from the growth-inhibitory effects of TGF beta 1.
Sipes
N J
NJ
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Miller
D A
DA
Bascom
C C
CC
Winkler
J K
JK
Matrisian
L M
LM
Moses
H L
HL
D000818:Animals; D002277:Carcinoma / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004247:DNA / Q000235:genetics; D004351:Drug Resistance; D004790:Enzyme Induction; D006801:Humans; D007535:Isomerases / Q000096:biosynthesis* / Q000235:genetics; D015603:Keratinocytes; D007708:Kirsten murine sarcoma virus; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000473:pathology; D019704:Protein Disulfide-Isomerases; D011499:Protein Processing, Post-Translational; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004247:DNA; D007535:Isomerases; D019704:Protein Disulfide-Isomerases