MUC4, a Multifunctional Transmembrane Glycoprotein, Induces Oncogenic Transformation of NIH3T3 Mouse Fibroblast Cells

被引:48
作者
Bafna, Sangeeta
Singh, Ajay P.
Moniaux, Nicolas
Endy, James D. [2 ]
Meza, Jane L. [3 ]
Batra, Surinder K. [1 ]
机构
[1] Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Dept Biochem & Mol Biol, Omaha, NE 68198 USA
[2] Univ Nebraska, Med Ctr, Dept Genet Cell Biol & Anat, Omaha, NE 68198 USA
[3] Univ Nebraska, Med Ctr, Dept Prevent & Societal Med, Omaha, NE 68198 USA
关键词
D O I
10.1158/0008-5472.CAN-08-3135
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Numerous studies have established the association of MUC4 with the progression of cancer and metastasis. An aberrant expression of MUC4 is reported in precancerous lesions, indicating its early involvement in the disease process; however, its precise role in cellular transformation has not been explored. MUC4 contains many unique domains and is proposed to affect cell signaling pathways and behavior of the tumor cells. In the present study, to decipher the oncogenic potential of MUC4, we stably expressed the MUC4 mucin in NIH3T3 mouse fibroblast cells. Stable ectopic expression of MUC4 resulted in increased growth, colony formation, and motility of NIH3T3 cells in vitro and tumor formation in nude mice when cells were injected s.c. Microarray analysis showed increased expression of several growth-associated and mitochondrial energy production-associated genes in MUC4-expressing NIH3T3 cells. In addition, expression of MUC4 in NIH3T3 cells resulted in enhanced levels of oncoprotein ErbB2 and its phosphorylated form (pY(1248)-ErbB2). In conclusion, our studies provide the first evidence that MUC4 alone induces cellular transformation and indicates a novel role of MUC4 in cancer biology. [Cancer Res 2008;68(22):9231-8]
引用
收藏
页码:9231 / 9238
页数:8
相关论文
共 42 条
[1]  
Andrianifahanana M, 2001, CLIN CANCER RES, V7, P4033
[2]   Muc4/sialomucin complex, the intramembrane ErbB2 ligand, in cancer and epithelia: To protect and to survive [J].
Carraway, KL ;
Perez, A ;
Idris, N ;
Jepson, S ;
Arango, M ;
Komatsu, M ;
Haq, B ;
Price-Schiavi, SA ;
Zhang, J ;
Carraway, CAC .
PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 71, 2002, 71 :149-185
[3]   Structure, evolution, anal biology of the MUC4 mucin [J].
Chaturvedi, Pallavi ;
Singh, Ajay P. ;
Batra, Surinder K. .
FASEB JOURNAL, 2008, 22 (04) :966-981
[4]   MUC4 mucin interacts with and stabilizes the HER2 oncoprotein in human pancreatic cancer cells [J].
Chaturvedi, Pallavi ;
Singh, Ajay P. ;
Chakraborty, Subhankar ;
Chauhan, Subhash C. ;
Bafna, Sangeeta ;
Meza, Jane L. ;
Singh, Pankaj K. ;
Hollingsworth, Michael A. ;
Mehta, Parmender P. ;
Batra, Surinder K. .
CANCER RESEARCH, 2008, 68 (07) :2065-2070
[5]   MUC4 mucin potentiates pancreatic tumor cell proliferation, survival, and invasive properties and interferes with its interaction to extracellular matrix proteins [J].
Chaturvedi, Pallavi ;
Singh, Ajay P. ;
Moniaux, Nicolas ;
Senapati, Shantibhushan ;
Chakraborty, Subhankar ;
Meza, Jane L. ;
Batra, Surinder K. .
MOLECULAR CANCER RESEARCH, 2007, 5 (04) :309-320
[6]   Aberrant expression of MUC4 in ovarian carcinoma: diagnostic significance alone and in combination with MUC1 and MUC16 (CA125) [J].
Chauhan, Subhash C. ;
Singh, Ajay P. ;
Ruiz, Fernanda ;
Johansson, Sonny L. ;
Jain, Maneesh ;
Smith, Lynette M. ;
Moniaux, Nicolas ;
Batra, Surinder K. .
MODERN PATHOLOGY, 2006, 19 (10) :1386-1394
[7]   REGULATION AND EXPRESSION OF A GROWTH ARREST-SPECIFIC GENE (GAS5) DURING GROWTH, DIFFERENTIATION, AND DEVELOPMENT [J].
COCCIA, EM ;
CICALA, C ;
CHARLESWORTH, A ;
CICCARELLI, C ;
ROSSI, GB ;
PHILIPSON, L ;
SORRENTINO, V .
MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (08) :3514-3521
[8]   MUC4 is Upregulated in ovarian carcinoma effusions and differentiates carcinoma cells from mesothelial cell [J].
Davidson, Ben ;
Baekelandt, Mark ;
Shih, Le-Ming .
DIAGNOSTIC CYTOPATHOLOGY, 2007, 35 (12) :756-760
[9]  
Hanaoka J, 2001, CANCER-AM CANCER SOC, V92, P2148, DOI 10.1002/1097-0142(20011015)92:8<2148::AID-CNCR1557>3.0.CO
[10]  
2-6