Expression analysis of proline rich 15 (Prr15) in mouse and human gastrointestinal tumors.
Proline rich 15 (Prr15), which encodes a protein of unknown function, is expressed almost exclusively in postmitotic cells both during fetal development and in adult tissues, such as the intestinal epithelium and the testis. To determine if this specific expression is lost in intestinal neoplasias, we examined Prr15 expression by in situ hybridization (ISH) on mouse intestinal tumors caused by different gene mutations, and on human colorectal cancer (CRC) samples. Prr15/PRR15 expression was consistently observed in mouse gastrointestinal (GI) tumors caused by mutations in the Apc gene, as well as in several advanced stage human CRCs. In contrast, no Prr15 expression was detected in intestinal tumors derived from mice carrying mutations in the Smad3, Smad4, or Cdkn1b genes. These findings, combined with the fact that a majority of sporadic human CRCs carry APC mutations, strongly suggest that the expression of Prr15/PRR15 in mouse and human GI tumors is linked, directly or indirectly, to the absence of the APC protein or, more generally, to the disruption of the Wnt signaling pathway.
Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics (MPIMG), Berlin, Germany.
Dominique
D
Meunier
Kalicharan
K
Patra
Ron
R
Smits
Andrea
A
Hägebarth
Angela
A
Lüttges
Rolf
R
Jaussi
Matthew J
MJ
Wieduwilt
Leticia
L
Quintanilla-Fend
Heinz
H
Himmelbauer
Riccardo
R
Fodde
Reinald H
RH
Fundele
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism* / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015152:Blotting, Northern; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000502:physiology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D011392:Proline / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051900:Smad3 Protein / Q000502:physiology; D051901:Smad4 Protein / Q000502:physiology
D025601:Adenomatous Polyposis Coli Protein; C493961:Cdkn1b protein, mouse; D009687:Nuclear Proteins; C555231:PRR15 protein, human; D011506:Proteins; D012334:RNA, Neoplasm; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D050760:Cyclin-Dependent Kinase Inhibitor p27; D011392:Proline