Stable and temperature-sensitive transformation of baby rat kidney cells by SV40 suppresses expression of membrane dipeptidase.
Membrane dipeptidase (MDP) is a zinc metalloenzyme located in the lungs and on the brush border membranes of the kidney and intestine. The gene for MDP (also termed DPEP1) is both frequently lost in Wilm's tumours and is located on human chromosome 16q24.3, a region of the genome known to contain a tumour suppressor gene(s). We now report on the regulation of MDP gene expression in normal and transformed cells. MDP enzyme activity and mRNA was detected in primary baby rat kidney (BRK) cells maintained in culture for up to 4 weeks. In contrast all stable transformed cell lines that were tested, derived either by transformation with the DNA tumour viruses SV40 or adenovirus, or in human tumour cell lines, contained very low levels of or no detectable MDP mRNA or enzyme activity. In BRK cells transformed by the temperature-sensitive tsA58 mutant of SV40 T antigen, MDP activity was not detectable, in cell lines grown at the permissive temperature (33 degrees C) but after 5-14 days of incubation at the non-permissive temperature (39.5 degrees C), MDP protein and enzyme activity could be readily detected. Taken together, these results indicate that MDP expression is characteristic of differentiated kidney epithelial cells and is down-regulated in proliferating, transformed cells.
Keynan
S
S
Department of Biochemistry and Molecular Biology, University of Leeds, UK.
Asipu
A
A
Hooper
N M
NM
Turner
A J
AJ
Blair
G E
GE
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D002462:Cell Membrane / Q000201:enzymology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002885:Chromosomes, Human, Pair 16; D004150:Dipeptidases / Q000378:metabolism*; D058851:GPI-Linked Proteins; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007668:Kidney / Q000201:enzymology*; D008667:Metalloproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D051381:Rats; D013539:Simian virus 40; D013997:Time Factors
D000952:Antigens, Polyomavirus Transforming; D058851:GPI-Linked Proteins; D008667:Metalloproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D004150:Dipeptidases; C038937:dipeptidase; C549872:dipeptidase 1