KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers

Corson, Timothy W.; Huang, Annie; Tsao, Ming‐Sound; Gallie, Brenda L.

doi:10.1038/sj.onc.1208641

Cited by 165 publications

(183 citation statements)

References 39 publications

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“…It was interesting to see that, to the exception of PLU-1/JARID1B (Lu et al, 1999), all the genes identified in our study were newly proposed as candidate cancer genes. Furthermore, MUC1 (Schroeder et al, 2004), a long known cell surface marker overexpressed in a sizeable fraction of breast tumours, and KIF14 (Corson et al, 2005), a recently proposed candidate at 1q31, presented DSs below the threshold and were excluded from our selection. Genes selected in our study belong to rather diverse functional groups, of which three appeared prevalent.…”

Section: Discussionmentioning

confidence: 99%

Genetic profiling of chromosome 1 in breast cancer: mapping of regions of gains and losses and identification of candidate genes on 1q

et al. 2006

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Chromosome 1 is involved in quantitative anomalies in 50 -60% of breast tumours. However, the structure of these anomalies and the identity of the affected genes remain to be determined. To characterise these anomalies and define their consequences on gene expression, we undertook a study combining array-CGH analysis and expression profiling using specialised arrays. Array-CGH data showed that 1p was predominantly involved in losses and 1q almost exclusively in gains. Noticeably, high magnitude amplification was infrequent. In an attempt to fine map regions of copy number changes, we defined 19 shortest regions of overlap (SROs) for gains (one at 1p and 18 at 1q) and of 20 SROs for losses (all at 1p). These SROs, whose sizes ranged from 170 kb to 3.2 Mb, represented the smallest genomic intervals possible based on the resolution of our array. The elevated incidence of gains at 1q, added to the wellestablished concordance between DNA copy increase and augmented RNA expression, made us focus on gene expression changes at this chromosomal arm. To identify candidate oncogenes, we studied the RNA expression profiles of 307 genes located at 1q using a home-made built cDNA array. We identified 30 candidate genes showing significant overexpression correlated to copy number increase. In order to substantiate their involvement, RNA expression levels of these candidate genes were measured by quantitative (Q)-RT -PCR in a panel of 25 breast cancer cell lines previously typed by array-CGH. Q -PCR showed that 11 genes were significantly overexpressed in the presence of a genomic gain in these cell lines, and 20 overexpressed when compared to normal breast.

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Section: Discussionmentioning

confidence: 99%

Genetic profiling of chromosome 1 in breast cancer: mapping of regions of gains and losses and identification of candidate genes on 1q

et al. 2006

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“…2 Reverse transcription (RT)-PCR expression analyses of all genes in this region showed that only KIF14 (kinesin family member 14), a poorly characterized kinesin, was overexpressed 31-to 92-fold in 4 breast cancer cell lines compared with healthy breast tissue. Robust, cell line-specific protein expression, paralleling the mRNA level, was confirmed by immunoblot.…”

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confidence: 99%

“…Among the lung tumors, KIF14 mRNA overexpression showed a strong trend toward association with decreased survival. 2 Although cloned several years ago, 3 KIF14's cellular function is not yet clear. A recent report indicates that KIF14 inhibition causes a delay in the metaphase-to-anaphase transition, characterized by misaligned chromosomes that oscillate abnormally between the spindle pole body and the metaphase plate.…”

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confidence: 99%

“…Our analyses in lung tumors also suggest that KIF14 expression may be a predictor of patient outcome. 2 Moreover, as a kinesin, and thus an ATPase enzyme, KIF14 is an attractive therapeutic target. In the present study, we demonstrate for the first time KIF14 overexpression in primary breast tumors, and show that KIF14 expression is prognostic for patient outcome in breast cancer.…”

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KIF14 mRNA expression is a predictor of grade and outcome in breast cancer

Corson

Gallie

2006

Intl Journal of Cancer

105

103

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Gain of chromosome 1q is a hallmark of breast cancer, and likely reflects oncogene amplification. We previously identified mitotic kinesin KIF14 (kinesin family member 14) as an overexpressed candidate oncogene in the 1q31.3-1q32.1 minimal region of genomic gain in breast cancer cell lines. KIF14 also showed high expression in other cancers, notably an association with survival in lung tumors. We now report KIF14 expression in 99 primary breast tumors and 10 normal breast controls. Measured by realtime RT-PCR, KIF14 was overexpressed 10-fold on average in tumors relative to normals (t test p 5 0.000054); expression increased with grade (ANOVA p 5 0.000006). Infiltrating ductal carcinomas had higher KIF14 levels than lobular (p 5 0.017), and estrogen receptor (ER) negative tumors had higher KIF14 levels than ER positive tumors (t test p 5 0.030). KIF14 expression correlated positively with Ki-67 mRNA level (Spearman r 5 0.692, p 5 0.000001), fraction of positive nodes (r 5 0.227, p 5 0.024) and percent invasive cells (r 5 0.360, p 5 0.0002), and negatively with percent fatty stroma (r 5 20.258, p 5 0.010) and percent normal epithelium (r 5 20.291, p 5 0.003). KIF14 expression is thus tumor-specific and increased in more aggressive tumors. Indeed, KIF14 expression predicted overall survival (univariate Cox p 5 0.010), with an odds ratio of 3.60 (1.37-9.48), in 50 tumors with available outcome data. KIF14 overexpression also predicted decreased disease-free survival (log-rank p 5 0.049). These findings are the first evidence of association between expression of a mitotic kinesin and prognostic variables in breast cancer. ' 2006 Wiley-Liss, Inc.Key words: breast cancer; KIF14; kinesin; prognosis; real-time RT-PCR Recurrent chromosomal gains and losses are a feature of most cancers, and are presumed to reflect underlying oncogene amplification and tumor suppressor gene loss, respectively. In breast cancer, gain of 1q is the second-most common genomic gain (after 8q). Based on cumulative data in the Progenetix database of cytogenetic changes in cancer, 1 the minimal common region of genomic gain encompasses bands 1q31-1q32, gained or amplified in 44% of the 631 breast tumors in the database. 1 Gain of the long arm of chromosome 1 is one of the most frequent genomic aberrations in many tumor types, including retinoblastoma, strongly suggesting the presence of oncogene(s) in this region.Using quantitative multiplex PCR of genetic markers across the 1q31-1q32 region of chromosomal gain, we previously scanned DNA from 55 retinoblastoma and 12 breast cancer cell lines, and identified a 3.06 Mbp minimal region of gain. 2 Reverse transcription (RT)-PCR expression analyses of all genes in this region showed that only KIF14 (kinesin family member 14), a poorly characterized kinesin, was overexpressed 31-to 92-fold in 4 breast cancer cell lines compared with healthy breast tissue. Robust, cell line-specific protein expression, paralleling the mRNA level, was confirmed by immunoblot. KIF14 mRNA was also highly overexpressed in ...

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“…45,46 KIF14 is a microtubule motor that is amplified and overexpressed in breast cancer, lung cancer, and retinoblastoma. 15,47 It has been demonstrated that altered KIF14 mRNA expression is a prognostic indicator for patients with breast cancer and lung cancer. 15,17 The absence of KIF14 in HeLa cells reportedly resulted in a failure to complete cytokinesis, producing binucleated cells that underwent apoptosis after failed mitosis.…”

Section: Kinesin-2 Familymentioning

confidence: 99%

The role of kinesin family proteins in tumorigenesis and progression

Feng

2010

Cancer

113

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The kinesin superfamily contains a conserved class of microtubule-dependent molecular motor proteins that possess an adenosine triphosphatase activity and motion characteristics. The active movement of kinesins supports several cellular functions, including mitosis, meiosis, and the transport of macromolecules. Mitosis is a process of eukaryotic cell division that involves the division of nuclei, cytoplasm, organelles, and the cell membrane into 2 daughter cells with roughly equivalent portions of these cellular components. Any errors in this process could result in cell death, abnormality (such as gene deletion, chromosome translocation, or duplication), and cancer. Because mitosis is complex and highly regulated, alteration of kinesin expression or function could lead to carcinogenesis. Moreover, because human cancer is a gene-related disease involving abnormal cell growth, targeting kinesins may create a novel strategy for the control of human cancer. Indeed, several such drugs are being tested successfully in the clinic. In this review, the authors discuss in detail the structure and function of kinesins, the correlation of kinesin expression with tumorigenesis and progression, and the development of biomarkers and cancer-targeted therapy involving the kinesin family proteins. Cancer 2010;116:5150-60.

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KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers

Cited by 165 publications

References 39 publications

Genetic profiling of chromosome 1 in breast cancer: mapping of regions of gains and losses and identification of candidate genes on 1q

Genetic profiling of chromosome 1 in breast cancer: mapping of regions of gains and losses and identification of candidate genes on 1q

KIF14 mRNA expression is a predictor of grade and outcome in breast cancer

The role of kinesin family proteins in tumorigenesis and progression

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