Open AccessJournal Article
Mutational Analysis of the Candidate Tumor Suppressor Genes TEL and KIP1 in Childhood Acute Lymphoblastic Leukemia
Kimberly Stegmaier,Seisho Takeuchi,Todd R. Golub,Stefan K. Bohlander,Claus R. Bartram,H. Phillip Koeffler,D. Gary Gilliland +6 more
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TLDR
The exon organization of the TEL gene is determined and mutational analysis of TEL and KIP1 are performed in 33 childhood ALL patients known to have loss of heterozygosity at this locus; this suggest that neither TEL nor Kip1 is the critical 12p tumor suppressor gene in childhood ALL.Abstract:
We have shown previously that loss of heterozygosity at chromosome band 12p13 is among the most frequent genetic abnormalities identified in acute lymphoblastic leukemia (ALL) of childhood. Two known genes map within the critically deleted region of 12p: TEL, the gene encoding a new member of the ETS family of transcription factors, which is rearranged in a variety of hematological malignancies; and KIP1, the gene encoding the cyclin-dependent kinase inhibitor p27. Both genes are, therefore, excellent candidate tumor suppressor genes. In this report, we determined the exon organization of the TEL gene and performed mutational analysis of TEL and KIP1 in 33 childhood ALL patients known to have loss of heterozygosity at this locus. No mutations in either TEL or KIP1 were found; this suggests that neither TEL nor KIP1 is the critical 12p tumor suppressor gene in childhood ALL.read more
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Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas.
Massimo Loda,Barry Cukor,Sun W. Tam,Phillip T. Lavin,Michelangelo Fiorentino,Giulio Draetta,J. M. Jessup,Michele Pagano,Michele Pagano +8 more
TL;DR: It was found that carcinomas with low or absent p27 protein displayed enhanced proteolytic activity specific for p27, suggesting that low p27 expression can result from increased proteasome-mediated degradation rather than altered gene expression.
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The murine gene p27Kip1 is haplo-insufficient for tumour suppression
Matthew L. Fero,Erin Randel,Kay E. Gurley,James M. Roberts,James M. Roberts,Christopher J. Kemp +5 more
TL;DR: It is shown that both p27 nullizygous and p27 heterozygous mice are predisposed to tumours in multiple tissues when challenged with γ-irradiation or a chemical carcinogen, therefore p27 is a multiple-tissue tumour suppressor in mice.
Journal ArticleDOI
The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338
Alastair J. King,Huaiyu Sun,Bruce Diaz,Darlene Barnard,Wenyan Miao,Shubha Bagrodia,Mark S. Marshall +6 more
TL;DR: The results indicate that signal transduction through Raf-1 depends on both Ras and the activation of the Pak pathway, and a mechanism could exist through which one Ras effector pathway can be influenced by another.
Journal Article
Prognostic role of the cyclin-dependent kinase inhibitor p27 in non-small cell lung cancer.
Esposito,Alfonso Baldi,De Luca A,A. M. Groger,Massimo Loda,Giordano G,Mario Caputi,Feliciano Baldi,Michele Pagano,Antonio Giordano +9 more
TL;DR: P27 protein expression was found to be a prognostic factor correlating with the overall survival times and confirmation of the involvement of the proteasome-mediated proteolysis in p27 degradation should stimulate new strategies of nonsurgical treatments of non-small cell lung cancer.
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FoxM1: at the crossroads of ageing and cancer.
TL;DR: Observations suggest that interference with FoxM1 activity may contribute to the increase in mitotic errors seen in human diseases such as cancer and early onset of ageing diseases.
References
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Journal ArticleDOI
A cell cycle regulator potentially involved in genesis of many tumor types
Alexander Kamb,Nelleke A. Gruis,Jane Weaver-Feldhaus,Qingyun Liu,Keith D Harshman,Sean V. Tavtigian,Elisabeth Stockert,Rufus S. Day,Bruce E. Johnson,Mark H. Skolnick,Mark H. Skolnick +10 more
TL;DR: Findings suggest that MTS1 mutations are involved in tumor formation in a wide range of tissues.
Journal ArticleDOI
A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma
Stephen H. Friend,Stephen H. Friend,René Bernards,Snezna Rogelj,Robert A. Weinberg,Joyce M. Rapaport,Daniel M. Albert,Thaddeus P. Dryja +7 more
TL;DR: The isolation of a complementary DNA segment that detects a chromosomal segment having the properties of the gene at this locus is described, which is expressed in many tumour types, but no RNA transcript has been found in retinoblastomas and osteosarcomas.
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