Human PARM-1 is a novel mucin-like, androgen-regulated gene exhibiting proliferative effects in prostate cancer cells.
In this paper we characterize hPARM-1, the human ortholog of rat PARM-1 (prostatic androgen-repressed message-1) and demonstrate its role in prostate cancer. Immunofluorescence microscopy and ultrastructural analysis revealed the localization of hPARM-1 to Golgi, plasma membrane and the early endocytic pathway but not in lysosomes. Biochemical and deglycosylation studies showed hPARM-1 as a highly glycosylated, mucin-like type I transmembrane protein. Analysis of expression of hPARM-1 in various human tissues revealed its presence in most human tissues with especially high expression in heart, kidney and placenta. Androgen controls the expression of the gene as a marked 7-fold increase is seen in the androgen-dependent prostate cancer cell line, LNCaP on androgen stimulation. This is further supported by its decrease in expression in CWR22 xenograft upon castration. Moreover, ectopic expression of hPARM-1 in PC3 prostate cancer cells increased colony formation, suggesting a probable role in cell proliferation. These results suggest that hPARM-1 may have a role in normal biology of the prostate cell and in prostate cancer.
Fladeby
Cathrine
C
Department of Molecular Biosciences, University of Oslo, Oslo, Norway.
Gupta
Shailly N
SN
Barois
Nicolas
N
Lorenzo
Petri I
PI
Simpson
Jeremy C
JC
Saatcioglu
Fahri
F
Bakke
Oddmund
O
D000595:Amino Acid Sequence; D000727:Androgen-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000728:Androgens / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020285:Cryoelectron Microscopy; D017931:DNA Primers; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
D000727:Androgen-Binding Protein; D000728:Androgens; D017931:DNA Primers; C527680:PARM1 protein, human