Psychometric properties of the DISABKIDS Chronic Generic Module (DCGM-37) when used in children undergoing treatment for cancer.

BACKGROUND: The aim was to evaluate data quality and psychometric properties of an instrument for measurement of health-related quality of life: DISABKIDS Chronic Generic Module (DCGM-37) used in school-aged children with cancer. METHODS: All school-children diagnosed with cancer in Sweden during a two-and-a-half year period were invited to participate in the study. Analysis was performed on combined data from two assessments, two and-a-half and five months after start of cancer treatment (n = 170). The instrument was examined with respect to feasibility, data quality, reliability and construct and criterion-based validity. RESULTS: Missing items per dimension ranged from 0 to 5.3 percent, with a majority below three percent. Cronbach's alpha values exceeded 0.70 for all dimensions. There was support for the suggested groupings of items into dimensions for all but six of the 36 items of the DCGM-37 included in this study. The instrument discriminated satisfactorily between diagnoses reflecting treatment burden. CONCLUSIONS: The results indicate satisfactory data quality and reliability of the DCGM-37 when used in children undergoing treatment for cancer. Evaluation of construct validity showed generally acceptable results, although not entirely supporting the suggested dimensionality. Continued psychometric evaluation in a larger sample of children during and after treatment for cancer is recommended.

Nuclear factor 1-C2 is regulated by prolactin and shows a distinct expression pattern in the mouse mammary epithelial cells during development.

We have previously demonstrated that the transcription factor nuclear factor (NF)1-C2 plays an important role in the mammary gland for the activation of the tumor suppressor gene p53. It also activates the milk genes carboxyl ester lipase and whey acidic protein, implying that NF1-C2 participates both in the establishment of a functional gland and in protection of the gland against tumorigenesis during proliferation. In this study, we have developed a new sensitive NF1-C2-specific antiserum for immunohistochemical analyses of the NF1-C2 distribution during mammary gland development. We show that the NF1-C2 protein is present in the epithelial compartment at the virgin stage and throughout mammary gland development. However, in the lactation stage the NF1-C2 protein levels strongly decreased, and many epithelial nuclei stained negative. In situ hybridization shows that NF1-C2 transcripts are expressed in the whole epithelium at pregnancy as well as the lactation stage, indicating that the reduction in protein levels is posttranscriptionally regulated. At involution, the NF1-C2 proteins are back to high levels. Based on studies using NMuMG cells and mammary tissue from heterozygous prolactin receptor knockout mice, we also demonstrate that prolactin has a direct effect in the maintenance of the NF1-C2 protein levels in the mammary epithelial nuclei at the virgin stage and during pregnancy. Hence, we have identified another transcription factor in the mammary gland, besides signal transducer and activator of transcription 5, through which prolactin may control mammary gland development. Furthermore, our data suggest a link between prolactin and p53 in the mammary gland, through NF1-C2.

The p53 tumor suppressor gene is regulated in vivo by nuclear factor 1-C2 in the mouse mammary gland during pregnancy.

The p53 tumor suppressor protein plays an important role in preventing cancer development by arresting or killing potential tumor cells. Downregulated p53 levels, or mutations within the p53 gene, leading to the loss of p53 activity, are found in many breast carcinomas. Here we demonstrate that the p53 gene is transcriptionally upregulated in the normal mouse mammary gland at midpregnancy. We show that the specific isoform nuclear factor 1-C2 (NF1-C2) plays an important role in this activation. Functional mutation of the NF1-binding site in the mouse p53 promoter resulted in a reduction of the gene expression to less than 30% in mammary epithelial cells. By the use of two powerful techniques, chromatin immunoprecipitation and oligonucleotide decoy, we verify the importance of NF1-C2 in p53 gene activation in vivo. These findings demonstrate a broader role for NF1-C2 in the mammary gland at midpregnancy, beyond its earlier reported activation of milk protein genes. We also demonstrate that NF1-A1 proteins are produced in the mouse mammary gland. However, due to their lower affinity to the NF1-binding site, these proteins are not involved in the transcriptional upregulation of p53 at midpregnancy. This paper constitutes the first report demonstrating the importance of NF1 proteins in the p53 gene activation in the mouse mammary gland. It is also the first time that p53 gene activation is coupled to a specific, endogenously expressed NF1 isoform.

Nuclear factor 1-C2 contributes to the tissue-specific activation of a milk protein gene in the differentiating mammary gland.

Members of the nuclear factor 1 (NF1) transcription factor family have been postulated to be involved in the regulation of milk genes. In this work we have been able to identify the splice variant NF1-C2 as an important member of a tissue-specific activating complex that regulates the milk gene encoding carboxyl ester lipase (CEL). Mutation of the NF1-binding site in the CEL gene promoter results in a drastic reduction of the gene expression to about 15% in mammary epithelial cells. Furthermore, we demonstrate that the NF1-C2 protein interacts with a higher affinity to the NF1-binding site in the CEL gene promoter than other NF1 family members do and that NF1-C2 in the mouse mammary gland is a phosphorylated protein. During development of the mouse mammary gland, binding of NF1-C2 to the CEL gene promoter is induced at midpregnancy, in correlation with the induction of CEL gene expression. The fact that the NF1-C2 involving complex remains throughout the lactation period and decreases during the weaning period, when the CEL gene is down-regulated, supports its importance in the regulation of CEL gene expression. To our knowledge, this is the first report identifying a specific, endogenously expressed NF1 isoform to be involved in the tissue-specific activation of a gene.