Identification of alternatively spliced TIMP-1 mRNA in cancer cell lines and colon cancer tissue.
TIMP-1 is a promising new candidate as a prognostic marker in colorectal and breast cancer. We now describe the discovery of two alternatively spliced variants of TIMP-1 mRNA. The two variants lacking exon 2 (del-2) and 5 (del-5), respectively, were identified in human cancer cell lines by RT-PCR. The del-2 variant was, furthermore, detected in extracts from 12 colorectal cancer tissue samples. By western blotting additional bands of lower molecular mass than full-length TIMP-1 were identified in tumor tissue, but not in plasma samples obtained from cancer patients. The two splice variants of TIMP-1 may hold important clinical information, and either alone or in combination with measurement of full-length TIMP-1 they may improve the prognostic and/or predictive value of TIMP-1 analyses.
Usher
P A
PA
Department of Veterinary Pathobiology, Faculty of Life Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark.
Sieuwerts
A M
AM
Bartels
A
A
Lademann
U
U
Nielsen
H J
HJ
Holten-Andersen
L
L
Foekens
J A
JA
Brünner
N
N
Offenberg
H
H
D017398:Alternative Splicing; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000378:metabolism; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D005091:Exons; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019715:Tissue Inhibitor of Metalloproteinase-1