PRR5 encodes a conserved proline-rich protein predominant in kidney: analysis of genomic organization, expression, and mutation status in breast and colorectal carcinomas.
Loss of heterozygosity on chromosome 22q13.31 is a frequent event during human breast and colorectal carcinogenesis. Herein we characterize a novel gene at chromosome 22q13.31 designated PRR5. Alternative promoter usage and splicing converge to generate five PRR5 transcript variants with maximum mRNA expression in kidney. In vitro transcription/translation demonstrated that the five variants generate three protein isoforms differing in their N-terminal length. Mutational analysis of PRR5 in human breast and colorectal tumors did not reveal somatic mutations. However, mRNA expression analyses revealed PRR5 overexpression in a majority of colorectal tumors but substantial downregulation of PRR5 expression in a subset of breast tumors and reduced expression in two breast cancer cell lines. Treatment with trichostatin A increased PRR5 mRNA levels in BT549 and MDA-MB-231 cells, whereas 5'-aza-2'-deoxycytidine induced expression in MDA-MB-231 cells only. Thus, PRR5 may represent a potential candidate tumor suppressor gene in breast cancer.
Johnstone
Cameron N
CN
Department of Medicine, Gastroenterology Division, University of Pennsylvania, Philadelphia, PA 19104, USA.
Castellví-Bel
Sergi
S
Chang
Laura M
LM
Sung
Raphael K
RK
Bowser
Mark J
MJ
Piqué
Josep M
JM
Castells
Antoni
A
Rustgi
Anil K
AK
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D017931:DNA Primers; D016678:Genome; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D012333:RNA, Messenger