Reg IV, a new member of the regenerating gene family, is overexpressed in colorectal carcinomas.
A better understanding of the mechanisms by which colon tumor cells are able to survive exposure to drugs would be valuable for the development of new therapeutic strategies. We used differential display-PCR to compare gene expression in the drug-sensitive HT-29 colon cancer cell line and 3 drug-resistant subpopulations derived from this parental cell line. One of the genes identified is a new gene, Regenerating IV gene (Reg IV), and was strongly overexpressed in HT-29 drug-resistant cells. Other drug-resistant cell lines expressed Reg IV at a high level, whereas a low expression was noted in sensitive cell lines. Northern blot and real-time PCR analysis showed that Reg IV is more strongly expressed in 71% of colorectal tumors (in particular in mucinous carcinomas) than in normal colon tissues. The comparison of Reg IV expression with that of other REG genes, Regenerating Ialpha or (Reg Ialpha), Regenerating Ibeta (Reg Ibeta) and Pancreatitis-associated protein (PAP), highlights its predominant expression in colorectal tumors. Reg IV mRNA-positive tumor cells display different phenotypes: mucus-secreting, enterocyte-like or undifferentiated. Interestingly, whereas Reg IV expression is low in normal colon, its level in normal small intestine is similar to that in some colorectal tumors. In normal tissue, Reg IV mRNA-positive cells are mostly enteroendocrine cells and goblet cells. Our results point out the potential role of Reg IV in colorectal tumors and its subsequent interest as a pronostic indicator of tumor survival.
Violette
Sabine
S
INSERM U505, Université Pierre et Marie Curie, Paris, France.
Festor
Estelle
E
Pandrea-Vasile
Ivona
I
Mitchell
Valérie
V
Adida
Colette
C
Dussaulx
Elisabeth
E
Lacorte
Jean-Marc
JM
Chambaz
Jean
J
Lacasa
Michel
M
Lesuffleur
Thécla
T
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism; D051847:Lithostathine; D008297:Male; D005810:Multigene Family; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins; D000073718:Pancreatitis-Associated Proteins; D015347:RNA Probes; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D037181:Lectins, C-Type; D051847:Lithostathine; D009419:Nerve Tissue Proteins; D000073718:Pancreatitis-Associated Proteins; C497617:REG1A protein, human; C000612141:REG3A protein, human; C428528:REG4 protein, human; D015347:RNA Probes; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D005472:Fluorouracil