Limits...
A novel 1p36.2 located gene, APITD1, with tumour-suppressive properties and a putative p53-binding domain, shows low expression in neuroblastoma tumours.

Krona C, Ejeskär K, Carén H, Abel F, Sjöberg RM, Martinsson T - Br. J. Cancer (2004)

Bottom Line: A reduced pattern of expression was also observed in a set of various tumour types.Furthermore, we determined the genomic organisation of APITD1.We suggest that low expression of this gene might interfere with the ability for apoptosis through the p53 pathway.

View Article: PubMed Central - PubMed

Affiliation: 1Department of Clinical Genetics, Institute for the Health of Women and Children, Göteborg University, Sahlgrenska University Hospital-East, SE-41685 Gothenburg, Sweden.

ABSTRACT
Neuroblastoma is characterised by a lack of TP53 mutations and no other tumour suppressor gene consistently inactivated has yet been identified in this childhood cancer form. Characterisation of a new gene, denoted APITD1, in the neuroblastoma tumour suppressor candidate region in chromosome 1p36.22 reveals that APITD1 contains a predicted TFIID-31 domain, representing the TATA box-binding protein-associated factor, TAF(II)31, which is required for p53-mediated transcription activation. Two different transcripts of this gene were shown to be ubiquitously expressed, one of them with an elevated expression in foetal tissues. Primary neuroblastoma tumours of all different stages showed either very weak or no measurable APITD1 expression, contrary to the level of expression observed in neuroblastoma cell lines. A reduced pattern of expression was also observed in a set of various tumour types. APITD1 was functionally tested by adding APITD1 mRNA to neuroblastoma cells, leading to the cell growth to be reduced up to 90% compared to control cells, suggesting APITD1 to have a role in a cell death pathway. Furthermore, we determined the genomic organisation of APITD1. Automated genomic DNA sequencing of the coding region of the gene as well as the promoter sequence in 44 neuroblastoma tumours did not reveal any loss-of-function mutations, indicating that mutations in APITD1 is not a common abnormality of neuroblastoma tumours. We suggest that low expression of this gene might interfere with the ability for apoptosis through the p53 pathway.

Show MeSH

Related in: MedlinePlus

RT–PCR expression analysis of transcripts A and B in APITD1. Amplification of APITD1 transcript A and APITD1 transcript B in each sample is compared to the amplification of ACTB. (A) Fairly ubiquitous expression of both transcripts in a set of normal adult and foetal tissues (CLONTECH). Lanes 1–24, PCR products from the indicated tissues. (B) Reduced expression of APITD1 gene products in neuroblastoma tumours of different stages compared to neuroblastoma cell lines and adult and foetal normal tissues (OriGene). The outcome of the patients, the stage of neuroblastoma and the status of chromosome 1p is indicated above the upper panel; NED, no evidence of disease; DOD, dead of disease; 1, 2, 2a, 3, 4 and 4S, stages of neuroblastoma; −, negative for 1p deletion; +, positive for 1p deletion; ±, uncertain result (based on FISH and microsatellite analysis). Lanes 1–17, neuroblastoma tumours; lanes 18–26, neuroblastoma cell lines and normal tissues as indicted above the panel. (C) Reduced expression of APITD1 gene products in various tumours. Lanes 1–14, tumours of various types as indicated above the panel.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2747717&req=5

fig5: RT–PCR expression analysis of transcripts A and B in APITD1. Amplification of APITD1 transcript A and APITD1 transcript B in each sample is compared to the amplification of ACTB. (A) Fairly ubiquitous expression of both transcripts in a set of normal adult and foetal tissues (CLONTECH). Lanes 1–24, PCR products from the indicated tissues. (B) Reduced expression of APITD1 gene products in neuroblastoma tumours of different stages compared to neuroblastoma cell lines and adult and foetal normal tissues (OriGene). The outcome of the patients, the stage of neuroblastoma and the status of chromosome 1p is indicated above the upper panel; NED, no evidence of disease; DOD, dead of disease; 1, 2, 2a, 3, 4 and 4S, stages of neuroblastoma; −, negative for 1p deletion; +, positive for 1p deletion; ±, uncertain result (based on FISH and microsatellite analysis). Lanes 1–17, neuroblastoma tumours; lanes 18–26, neuroblastoma cell lines and normal tissues as indicted above the panel. (C) Reduced expression of APITD1 gene products in various tumours. Lanes 1–14, tumours of various types as indicated above the panel.

Mentions: Both APITD1 transcripts were ubiquitously expressed in all tested normal tissues, with an especially high level of expression in the adult testis of both transcripts and in the adult kidney of transcript B. A low level of expression of transcript B was detected in the peripheral blood leukocyte and spleen from adult tissues, and in the skeletal muscle and thymus from foetal tissues (Figure 5AFigure 5


A novel 1p36.2 located gene, APITD1, with tumour-suppressive properties and a putative p53-binding domain, shows low expression in neuroblastoma tumours.

Krona C, Ejeskär K, Carén H, Abel F, Sjöberg RM, Martinsson T - Br. J. Cancer (2004)

RT–PCR expression analysis of transcripts A and B in APITD1. Amplification of APITD1 transcript A and APITD1 transcript B in each sample is compared to the amplification of ACTB. (A) Fairly ubiquitous expression of both transcripts in a set of normal adult and foetal tissues (CLONTECH). Lanes 1–24, PCR products from the indicated tissues. (B) Reduced expression of APITD1 gene products in neuroblastoma tumours of different stages compared to neuroblastoma cell lines and adult and foetal normal tissues (OriGene). The outcome of the patients, the stage of neuroblastoma and the status of chromosome 1p is indicated above the upper panel; NED, no evidence of disease; DOD, dead of disease; 1, 2, 2a, 3, 4 and 4S, stages of neuroblastoma; −, negative for 1p deletion; +, positive for 1p deletion; ±, uncertain result (based on FISH and microsatellite analysis). Lanes 1–17, neuroblastoma tumours; lanes 18–26, neuroblastoma cell lines and normal tissues as indicted above the panel. (C) Reduced expression of APITD1 gene products in various tumours. Lanes 1–14, tumours of various types as indicated above the panel.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747717&req=5

fig5: RT–PCR expression analysis of transcripts A and B in APITD1. Amplification of APITD1 transcript A and APITD1 transcript B in each sample is compared to the amplification of ACTB. (A) Fairly ubiquitous expression of both transcripts in a set of normal adult and foetal tissues (CLONTECH). Lanes 1–24, PCR products from the indicated tissues. (B) Reduced expression of APITD1 gene products in neuroblastoma tumours of different stages compared to neuroblastoma cell lines and adult and foetal normal tissues (OriGene). The outcome of the patients, the stage of neuroblastoma and the status of chromosome 1p is indicated above the upper panel; NED, no evidence of disease; DOD, dead of disease; 1, 2, 2a, 3, 4 and 4S, stages of neuroblastoma; −, negative for 1p deletion; +, positive for 1p deletion; ±, uncertain result (based on FISH and microsatellite analysis). Lanes 1–17, neuroblastoma tumours; lanes 18–26, neuroblastoma cell lines and normal tissues as indicted above the panel. (C) Reduced expression of APITD1 gene products in various tumours. Lanes 1–14, tumours of various types as indicated above the panel.
Mentions: Both APITD1 transcripts were ubiquitously expressed in all tested normal tissues, with an especially high level of expression in the adult testis of both transcripts and in the adult kidney of transcript B. A low level of expression of transcript B was detected in the peripheral blood leukocyte and spleen from adult tissues, and in the skeletal muscle and thymus from foetal tissues (Figure 5AFigure 5

Bottom Line: A reduced pattern of expression was also observed in a set of various tumour types.Furthermore, we determined the genomic organisation of APITD1.We suggest that low expression of this gene might interfere with the ability for apoptosis through the p53 pathway.

View Article: PubMed Central - PubMed

Affiliation: 1Department of Clinical Genetics, Institute for the Health of Women and Children, Göteborg University, Sahlgrenska University Hospital-East, SE-41685 Gothenburg, Sweden.

ABSTRACT
Neuroblastoma is characterised by a lack of TP53 mutations and no other tumour suppressor gene consistently inactivated has yet been identified in this childhood cancer form. Characterisation of a new gene, denoted APITD1, in the neuroblastoma tumour suppressor candidate region in chromosome 1p36.22 reveals that APITD1 contains a predicted TFIID-31 domain, representing the TATA box-binding protein-associated factor, TAF(II)31, which is required for p53-mediated transcription activation. Two different transcripts of this gene were shown to be ubiquitously expressed, one of them with an elevated expression in foetal tissues. Primary neuroblastoma tumours of all different stages showed either very weak or no measurable APITD1 expression, contrary to the level of expression observed in neuroblastoma cell lines. A reduced pattern of expression was also observed in a set of various tumour types. APITD1 was functionally tested by adding APITD1 mRNA to neuroblastoma cells, leading to the cell growth to be reduced up to 90% compared to control cells, suggesting APITD1 to have a role in a cell death pathway. Furthermore, we determined the genomic organisation of APITD1. Automated genomic DNA sequencing of the coding region of the gene as well as the promoter sequence in 44 neuroblastoma tumours did not reveal any loss-of-function mutations, indicating that mutations in APITD1 is not a common abnormality of neuroblastoma tumours. We suggest that low expression of this gene might interfere with the ability for apoptosis through the p53 pathway.

Show MeSH
Related in: MedlinePlus