Abstract:
:Induction of differentiation in a variety of model systems is accompanied by cell cycle exit and inhibition of Cdk2 kinase activity. We asked whether inhibition of Cdk2 activity is sufficient to allow differentiation to occur in a non-small cell lung cancer cell line. Treatment of NCI-H358 with flavopiridol, an inhibitor of multiple Cdk's, resulted in growth arrest and induction of mucinous differentiation. The onset of differentiation coincided temporally with loss of Cdk2 kinase activity. Western analysis revealed that flavopiridol treatment resulted in depletion of both cyclin E and D1, suggesting that loss of the regulatory subunits is at least partially responsible for the loss of Cdk kinase activity. Similarly, roscovitine, an inhibitor of Cdk's 1, 2, and 5, but not Cdk4, also induced differentiation in NCI-H358, although the resulting pattern of expression of cell cycle regulatory genes differed from the pattern obtained with flavopiridol. Furthermore, stable expression of an antisense Cdk2 construct in NCI-H358 also resulted in the appearance of a marker of mucinous differentiation. These results show that the inhibition of activity of cyclin dependent kinases, particularly Cdk2, by multiple different mechanisms is accompanied by differentiation. Thus, induction of differentiation is one potential mechanism of action for agents that down-regulate Cdk activity.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Lee HR,Chang TH,Tebalt MJ 3rd,Senderowicz AM,Szabo Ekeywords:
subject
Has Abstractpub_date
1999-07-01 00:00:00pages
161-6issue
1eissn
1019-6439issn
1791-2423journal_volume
15pub_type
杂志文章abstract::Although CD138 expression is a hallmark of plasma cells and myeloma cells, reduced CD138 expression is occasionally found. However, the mechanisms underlying CD138 downregulation in myeloma cells remain unclear. Previous reports suggest that the bone marrow microenvironment may contribute to CD138 downregulation. Amon...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.2134
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abstract::CD26 is a surface glycoprotein with intrinsic dipeptidyl peptidase IV (DPPIV) enzyme activity with multiple biological roles, including being intricately involved in immunoregulation as a T-cell activation molecule and as a regulator of chemokine function. T-cell lymphoid malignancies represent a heterogeneous group o...
journal_title:International journal of oncology
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journal_title:International journal of oncology
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journal_title:International journal of oncology
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journal_title:International journal of oncology
pub_type: 杂志文章,评审
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abstract::Tissue samples from a malignant melanoma of the anal canal and its local metastasis were short-term cultured and analyzed cytogenetically. Complex chromosome aberrations were found in the primary tumor, yielding the karyotype 49-50,X,-Y,der(1)t(1;13)(q44;q12),+der(2)t(2;8) (q31;q12),der(6)t(5;6)(q13;q21),+del(6)(q12q2...
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pub_type: 杂志文章
doi:10.3892/ijo.2011.1005
更新日期:2011-07-01 00:00:00
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journal_title:International journal of oncology
pub_type: 临床试验,杂志文章
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更新日期:2002-06-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-11-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2003-04-01 00:00:00
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journal_title:International journal of oncology
pub_type: 临床试验,杂志文章
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更新日期:1998-09-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:10.3892/ijo.15.1.25
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pub_type: 杂志文章
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.8.6.1179
更新日期:1996-06-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-09-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3402
更新日期:2016-05-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
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journal_title:International journal of oncology
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2574
更新日期:2014-10-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00
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pub_type: 杂志文章
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journal_title:International journal of oncology
pub_type: 杂志文章
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