hnRNP B1 protein may be a possible prognostic factor in squamous cell carcinoma of the lung

Wu, Shulin; Sato, Masami; Endo, Chiaki; Sakurada, Akira; Dong, Boming; Aikawa, Hirokazu; Chen, Yan; Okada, Yoshinori; Matsumura, Y.; Sueoka, Eisaburo; Kondo, Takashi

doi:10.1016/s0169-5002(03)00226-5

Cited by 52 publications

(36 citation statements)

References 23 publications

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“…In squamous cell lung cancer high expression hnRNP B1 has also been shown to be associated with improved survival (Wu et al, 2003). Such observations indicate that certain hnRNP family members may be prognostic markers for colorectal cancer.…”

Section: Discussionmentioning

confidence: 90%

Heterogeneous nuclear ribonucleoprotein K is over expressed, aberrantly localised and is associated with poor prognosis in colorectal cancer

et al. 2006

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Heterogeneous ribonucleoprotein K (hnRNP K) is a member of the hnRNP family which has several different cellular roles including transcription, mRNA shuttling, RNA editing and translation. Several reports implicate hnRNP K having a role in tumorigenesis, for instance hnRNP K increases transcription of the oncogene c-myc and hnRNP K expression is regulated by the p53/MDM 2 pathway. In this study comparing normal colon to colorectal cancer by proteomics, hnRNP K was identified as being overexpressed in this type of cancer. Immunohistochemistry with a monoclonal antibody to hnRNP K (which we developed) on colorectal cancer tissue microarray, confirmed that hnRNP K was overexpressed in colorectal cancer (Po0.001) and also showed that hnRNP K had an aberrant subcellular localisation in cancer cells. In normal colon hnRNP K was exclusively nuclear whereas in colorectal cancer the protein localised both in the cytoplasm and the nucleus. There were significant increases in both nuclear (P ¼ 0.007) and cytoplasmic (P ¼ 0.001) expression of hnRNP K in Dukes C tumours compared with early stage tumours. In Dukes C patient's good survival was associated with increased hnRNP K nuclear expression (P ¼ 0.0093). To elaborate on the recent observation that hnRNP K is regulated by p53, the expression profiles of these two proteins were also analysed. There was no correlation between hnRNP K and p53 expression, however, patients who presented tumours that were positive for hnRNP K and p53 had a poorer survival outcome (P ¼ 0.045).

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Section: Discussionmentioning

confidence: 90%

Heterogeneous nuclear ribonucleoprotein K is over expressed, aberrantly localised and is associated with poor prognosis in colorectal cancer

et al. 2006

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“…Importantly, hnRNP A1 has been shown to be up-regulated in a wide variety of cancers, including breast, colorectal, and lung, and, as described above, gliomas (Pino et al 2003;Ushigome et al 2005;Li et al 2009;David et al 2010). Likewise, hnRNP A2 is consistently overexpressed in a wide range of cancers (Zhou et al 2001;Yan-Sanders et al 2002;Wu et al 2003). hnRNP A2 is expressed at high levels during mouse lung development, then down-regulated in the adult lung, indicating an important role during highly proliferative periods of normal development and confirming the connection between proliferation and hnRNP A2 up-regulation (Montuenga et al 1998).…”

Section: Hnrnp and Sr Proteins In Proliferation And Cancermentioning

confidence: 87%

Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged

David

Manley²

2010

Genes Dev.

727

667

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Alternative splicing of mRNA precursors is a nearly ubiquitous and extremely flexible point of gene control in humans. It provides cells with the opportunity to create protein isoforms of differing, even opposing, functions from a single gene. Cancer cells often take advantage of this flexibility to produce proteins that promote growth and survival. Many of the isoforms produced in this manner are developmentally regulated and are preferentially re-expressed in tumors. Emerging insights into this process indicate that pathways that are frequently deregulated in cancer often play important roles in promoting aberrant splicing, which in turn contributes to all aspects of tumor biology.

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“…A number of studies suggest that hnRNP A2/B1 proteins are overexpressed in a variety of cancers and may be useful markers for screening for breast, pancreatic, non-small cell lung cancers and oral squamous cell carcinoma Sueoka et al, 1999;Sueoka et al, 2001;Tockman et al, 1997;Wu et al, 2003;Yan-Sanders et al, 2002;Zhou et al, 2001a;Zhou et al, 1996;Zhou et al, 2001b). A recent study showed that these proteins are also potentially new broad targets in cancer therapeutics as cancer cells with simultaneously lowered levels of hnRNPs A1 and A2 underwent apoptosis (Patry et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Roles of heterogeneous nuclear ribonucleoproteins A and B in cell proliferation

Brown

Rothnagel

et al. 2005

Journal of Cell Science

110

114

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IntroductionHeterogeneous nuclear ribonucleoprotein particle proteins (hnRNPs) are abundant, multi-tasking proteins that play a central role in RNA metabolism. They are involved in packaging nascent hnRNA, alternative RNA splicing, mRNA export from the nucleus, and cytoplasmic trafficking, stability and translation (Dreyfuss et al., 2002;Krecic and Swanson, 1999;Shyu and Wilkinson, 2000;Weighardt et al., 1996). They also have an as yet poorly defined role in telomere maintenance.More than 20 hnRNPs, many of which are characterised by possession of RNA-recognition motifs (RRMs), have been identified. The hnRNPs A/B are the major components of the 40S particles that package hnRNA. This packaging was originally envisaged to mimic that of histones in nucleosomes but this analogy appears to be inappropriate as the levels of the core proteins are not stoichiometric: they differ markedly between cell types, and their association with RNA is dependent on the nucleic acid sequence (Dreyfuss et al., 1993). However, given the role of these core particles in hnRNA packaging one might anticipate a correlation between the abundance of their proteins and the transcriptional activity in the cell. This is borne out experimentally: there is a marked difference in the concentration of hnRNP A1 between resting or slowly dividing cells and rapidly dividing cells. In the latter, hnRNPs A1 and A2 have been proposed to be present at similar levels. But hnRNP A1, which is abundant in a range of human, hamster and mouse proliferating cells, is present at markedly lower levels in confluent or resting cells, whereas hnRNP A2 is less affected (Celis et al., 1986;LeStourgeon, 1978).The levels of hnRNPs A/B differ not only between proliferating and resting cells: some also fluctuate during the cell cycle (Leser and Martin, 1987;Minoo et al., 1989). In HeLa cells hnRNPs A2 and B1 are synthesized in the G1 phase, and their levels fall in G2 and M phases, with hnRNP B1 protein level falling more markedly . The relative and absolute levels of these two proteins also differ markedly between tissues, both being particularly abundant in rat brain, testis, lung, spleen and ovary (Kamma et al., 1999;Ma et al., 2002).Many genes show a correlation between strong expression in proliferating cancer cells and the fluctuations in the protein level across the cell cycle (Dreyfuss et al., 1993;Whitfield et al., 2002). The levels of hnRNP A/B proteins are of particular interest as it has been suggested that upregulation of some members of this protein family is associated, as either a cause or consequence, with cellular proliferation and cancer. The hnRNP A2 and its longer B1 isoform are expressed at an early stage in a variety of tumours and have been proposed as early markers for cancer, especially lung cancer (Fielding et al., 1999;Mulshine et al., 2002;Pino et al., 2003;Sueoka et al., 1999;Whitfield et al., 2002;Zhou et al., 1996) and possibly breast cancer (Zhou et al., 2001a). The upregulation of hnRNP A2/B1 in cancer parallels its expression in lung dev...

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hnRNP B1 protein may be a possible prognostic factor in squamous cell carcinoma of the lung

Cited by 52 publications

References 23 publications

Heterogeneous nuclear ribonucleoprotein K is over expressed, aberrantly localised and is associated with poor prognosis in colorectal cancer

Heterogeneous nuclear ribonucleoprotein K is over expressed, aberrantly localised and is associated with poor prognosis in colorectal cancer

Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged

Roles of heterogeneous nuclear ribonucleoproteins A and B in cell proliferation

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