Altered expression and localization of creatine kinase B, heterogeneous nuclear ribonucleoprotein F, and high mobility group box 1 protein in the nuclear matrix associated with colon cancer

被引:76
作者
Balasubramani, M
Day, BW
Schoen, RE
Getzenberg, RH
机构
[1] Johns Hopkins Univ Hosp, Brady Urol Res Inst, Baltimore, MD 21287 USA
[2] Univ Pittsburgh, Sch Med, Dept Urol, Pittsburgh, PA USA
[3] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA USA
[4] Univ Pittsburgh, Dept Chem, Pittsburgh, PA USA
[5] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA
关键词
D O I
10.1158/0008-5472.CAN-05-3771
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Identification of biomarkers could lead to the development of effective screening tests for colorectal cancer. A previous study from our laboratory showed specific alterations of nuclear structure in colon cancer. In an effort to characterize these biomarkers, protein spots were selected from separations made by two-dimensional gel electrophoresis, which were analyzed by mass spectrometry. The sequences obtained from the isolated spots revealed that they have close similarity to creatine kinase B (CKB) isoforms, heterogeneous nuclear ribonucleoprotein F (hnRNP F) and high mobility group box 1 protein (HMGBI) isoforms. To determine the expression of these proteins in colon cancer, expression was studied in 9 tumor and matched adjacent normal pairs, 5 donor colons, 16 polyps, 4 metastatic liver lesions and matched adjacent normal pairs, and 3 liver donors. CKB and hnRNP F were expressed in 78% and 89% of colon tumors, respectively. hnRNP F had a higher frequency of expression than CKB in premalignant polyps. With the establishment of differential expression of the proteins in colon cancer, their subcellular localization was analyzed. The subcellular fractions studied both showed high protein levels of hnRNP F in colon tumors compared with normal colon tissues. Surprisingly, subcellular levels of CKB were decreased in colon tumors, suggesting that the observed high CKB levels in nuclear matrix extracts are caused by the enhanced localization of CKB to the nuclear matrix during colon tumorigenesis. These results suggest an involvement of hnRNP F and CKB in colorectal cancer. Additionally, they suggest that hnRNP F is a potential marker for colorectal cancer progression.
引用
收藏
页码:763 / 769
页数:7
相关论文
共 37 条
[31]   Proteome analysis reveals novel proteins associated with proliferation and differentiation of the colorectal cancer cell line Caco-2 [J].
Stierum, R ;
Gaspari, M ;
Dommels, Y ;
Ouatas, T ;
Pluk, H ;
Jespersen, S ;
Vogels, J ;
Verhoeckx, K ;
Groten, J ;
van Ommen, B .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 2003, 1650 (1-2) :73-91
[32]   NATURAL-HISTORY OF UNTREATED COLONIC POLYPS [J].
STRYKER, SJ ;
WOLFF, BG ;
CULP, CE ;
LIBBE, SD ;
ILSTRUP, DM ;
MACCARTY, RL .
GASTROENTEROLOGY, 1987, 93 (05) :1009-1013
[33]   Distinct cellular expressions of creatine synthetic enzyme GAMT and creatine kinases uCK-Mi and CK-B suggest a novel neuron-glial relationship for brain energy homeostasis [J].
Tachikawa, M ;
Fukaya, M ;
Terasaki, T ;
Ohtsuki, S ;
Watanabe, M .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2004, 20 (01) :144-160
[34]   RETRACTED: Functional characterization of the bladder cancer marker, BLCA-4 (Retracted article. See vol. 19, pg. 3327, 2013) [J].
Van Le, TS ;
Myers, J ;
Konety, BR ;
Barder, T ;
Getzenberg, RH .
CLINICAL CANCER RESEARCH, 2004, 10 (04) :1384-1391
[35]   hnRNP F influences binding of a 64-kilodalton subunit of cleavage stimulation factor to mRNA precursors in mouse B cells [J].
Veraldi, KL ;
Arhin, GK ;
Martincic, K ;
Chung-Ganster, LH ;
Wilusz, J ;
Milcarek, C .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (04) :1228-1238
[36]   Colorectal cancer screening - Scientific review [J].
Walsh, JME ;
Terdiman, JP .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2003, 289 (10) :1288-1296
[37]   Creatine kinase BB isoenzyme levels in tumour cytosols and survival of breast cancer patients [J].
Zarghami, N ;
Giai, M ;
Yu, H ;
Roagna, R ;
Ponzone, R ;
Katsaros, D ;
Sismondi, P ;
Diamandis, EP .
BRITISH JOURNAL OF CANCER, 1996, 73 (03) :386-390