ANALYSIS OF THE COMPLETE SEQUENCE OF THE NOVEL METASTASIS-ASSOCIATED CANDIDATE GENE, MTA1, DIFFERENTIALLY EXPRESSED IN MAMMARY ADENOCARCINOMA AND BREAST-CANCER CELL-LINES

被引：89

作者：

TOH, Y ^{[1
]}

PENCIL, SD ^{[1
]}

NICOLSON, GL ^{[1
]}

机构：

[1] UNIV TEXAS,MD ANDERSON CANC CTR,DEPT TUMOR BIOL,HOUSTON,TX 77030

来源：

GENE | 1995年 / 159卷 / 01期

关键词：

NEOPLASTIC INVASION; SRC HOMOLOGY; RAT; CDNA; SIGNAL TRANSDUCTION; AMINO ACID SEQUENCE; PHOSPHORYLATION SITE; SH3; BINDING;

D O I：

10.1016/0378-1119(94)00410-T

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

To understand the genes and gene products involved in breast cancer invasion and metastasis, we previously isolated ten differentially expressed genes by differential cDNA library screening techniques, using the 13762NF rat mammary adenocarcinoma metastatic system. In this study, we further analysed a novel candidate metastasis-associated gene, mta1, previously designated clone 10.14. Northern blotting analyses showed that the steady-state mRNA expression level of mtn1 was fourfold higher in a highly metastatic line (MTLn3) than in a nonmetastatic line (MTC.4). The mta1 gene was expressed at low levels in various normal rat organs, except testis, where it was expressed in high amounts. The mRNA expression levels of the human homologue of this gene were also examined in two human breast cancer metastatic systems; the ratios of mRNA were estimated to be MCF-7 (nonmetastatic):MCF7/LCC1 (invasive):MCF7/LCC2 (metastatic)=1:2:4 and MDA-MB-468 (nonmetastatic):MDA231 (metastatic)=1:4. Thus, the expression of this gene directly correlated with metastatic potential in two human systems, as well as in the rat metastatic system. Clone 10.14 was used to isolate a full-length cDNA clone for mta1, yielding the clone p10.14-C4.5, which was sequenced and analysed. Clone p10.14-C4.5 was 2756-bp long and contained a single open reading frame that could encode a protein of 703 amino acid (aa) residues. The aa sequence of mta1 was found to be novel by database homology search and contained possible phosphorylation sites for tyrosine kinase, protein kinase C and casein kinase II. A Pro-rich stretch was found at the C-terminal end that completely matched the consensus sequence for the SH3-binding motif. Thus, the novel gene mta1 may encode an important molecule that is functional in breast cancer invasion and metastasis, and could prove to be a useful probe to assess the malignancy of breast cancers.

引用

页码：97 / 104

页数：8

共 40 条

[1] Alberts, Bray, Lewis, Raff, Roberts, Watson, Molecular Biology of the Cell, Germ Cells and Fertilization, pp. 839-878, (1989)
[2] Atnip, Carter, Nicolson, Dabbous, Chemotactic response of rat mammary adenocarcinoma cell clones to tumor-derived cytokines, Biochem. Biophys. Res. Commun., 146, pp. 996-1002, (1987)
[3] Basset, Bellocq, Wolf, Stoll, Hutin, Limacher, Podhajcer, Chenard, Rio, Chambon, A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas, Nature, 348, pp. 699-704, (1990)
[4] Chambers, Ras-responsive genes and tumor metastasis, Crit. Rev. Oncogenesis, 4, pp. 95-114, (1993)
[5] Cooper, Esch, Tayler, Hunter, Phosphorylation sites in enolase and lactase dehydrogenase utilized by tyrosine protein kinase in vivo and in vitro, J. Biol. Chem., 259, pp. 7835-7841, (1984)
[6] Dear, Ramshaw, Kefford, Differential expression of a novel gene, WDNM1, in nonmetastatic rat mammary adenocarcinoma cells, Cancer Res., 48, pp. 5203-5209, (1988)
[7] Dear, McDonald, Kefford, Transcriptional down-regulation of a rat gene, WDNM2, in metastatic DMBA-8 cells, Cancer Res., 49, pp. 5323-5328, (1989)
[8] Ebralidge, Tulchinsky, Grigorian, Afanasyeva, Senin, Revazova, Lukanidin, Isolation and characterization of a gene specifically expressed in different metastatic cells and whose deduced gene product has a high degree of homology to a Ca<sup>2+</sup>-binding protein family, Genes & Development, 3, pp. 1086-1093, (1989)
[9] Hunter, Synthetic peptide substrates for a tyrosine protein kinase, J. Biol. Chem., 257, pp. 4843-4848, (1982)
[10] Kishimoto, Nishiyama, Nakanishi, Uratsuji, Nomura, Takeyama, Nishizuka, Studies on the phosphorylation of myelin basic protein by protein kinase C and adenosine 3':5'-monophosphate-dependent protein kinase, J. Biol. Chem., 260, pp. 12492-12499, (1985)

← 1 2 3 4 →