The novel tumour suppressor gene ING1 is overexpressed in human melanoma cell lines

被引:29
作者
Campos, EI
Cheung, KJJ
Murray, A
Li, S
Li, G
机构
[1] Univ British Columbia, Vancouver Hosp & Hlth Sci Ctr, Dept Med, Div Dermatol, Vancouver, BC V5Z 1M9, Canada
[2] Univ British Columbia, Vancouver Hosp & Hlth Sci Ctr, Dept Med Genet, Vancouver, BC V5Z 1M9, Canada
关键词
DNA sequencing; mutation; melanoma; p33(ING1); single-strand conformation polymorphism analysis;
D O I
10.1046/j.1365-2133.2002.04641.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Background Epidemiological evidence indicates that exposure to ultraviolet (UV) radiation is directly linked to the increase of both incidence and mortality of melanoma. However, the genetic changes caused by UV radiation that lead to melanoma formation remain poorly understood. Recently, a potential tumour suppressor gene ING1 (inhibitor of growth 1) was shown to inhibit cell growth and induce apoptosis in the presence of p53. We have demonstrated that the expression of ING1 is induced after UV irradiation and that ING1 enhances the repair of UV-damaged DNA. Objectives To investigate if ING1 plays a role in melanoma formation. Methods We examined p33(ING1) expression levels in 14 melanoma cell lines. Results We found that p33(ING1) is overexpressed at both mRNA and protein levels in melanoma cell lines compared with normal melanocytes. Single-strand conformation polymorphism (SSCP) analysis showed band shifting in two melanoma cell lines. DNA sequencing confirmed that there were nucleotide alterations in the ING1 gene in Sk-mel-24 and Sk-mel-110 cell lines. Two silent nucleotide alterations in exon la were detected in Sk-mel-110. In Sk-mel-24, the A --> G nucleotide alteration at codon 260 resulted in an amino acid change from Asn to Ser, while seven other nucleotide alterations were silent. To determine if the silent nucleotide alterations in these two melanoma cell lines were due to polymorphism, SSCP analysis of ING1 gene was performed in 25 healthy volunteers. No band shift was observed in the SSCP analysis, suggesting that the nucleotide alterations in the melanoma cell lines are unlikely to be due to polymorphism. Conclusions Taken together, our data demonstrate that ING1 is overexpressed, but infrequently mutated. in melanoma cell lines.
引用
收藏
页码:574 / 580
页数:7
相关论文
共 35 条
[1]  
Akslen LA, 1998, INT J CANCER, V79, P91
[2]   EXCISION REPAIR OF PYRIMIDINE DIMERS INDUCED BY SIMULATED SOLAR-RADIATION IN THE SKIN OF PATIENTS WITH BASAL-CELL CARCINOMA [J].
ALCALAY, J ;
FREEMAN, SE ;
GOLDBERG, LH ;
WOLF, JE .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1990, 95 (05) :506-509
[3]  
Brochez L, 2000, EUR J DERMATOL, V10, P71
[4]  
Cheung KJ, 2001, CANCER RES, V61, P4974
[5]   Expression of the novel tumour suppressor p33ING1 is independent of p53 [J].
Cheung, KJJ ;
Bush, JA ;
Jia, W ;
Li, G .
BRITISH JOURNAL OF CANCER, 2000, 83 (11) :1468-1472
[6]  
Essner R, 1998, CANCER, V82, P309, DOI 10.1002/(SICI)1097-0142(19980115)82:2<317::AID-CNCR10>3.0.CO
[7]  
2-1
[8]   On the spontaneous mutability of CpG sites in cultured S49 mouse lymphoma cells [J].
Gan, JP ;
Zhang, YL ;
Carter, KB ;
Cauthron, RD ;
Steinberg, RA .
SOMATIC CELL AND MOLECULAR GENETICS, 1999, 25 (03) :129-145
[9]   Suppression of the novel growth inhibitor p33(ING1) promotes neoplastic transformation [J].
Garkavtsev, I ;
Kazarov, A ;
Gudkov, A ;
Riabowol, K .
NATURE GENETICS, 1996, 14 (04) :415-420
[10]   The candidate tumour suppressor p33ING1 cooperates with p53 in cell growth control [J].
Garkavtsev, I ;
Grigorian, IA ;
Ossovskaya, VS ;
Chernov, MV ;
Chumakov, PM ;
Gudkov, AV .
NATURE, 1998, 391 (6664) :295-298