In this paper we describe how research on the mouse mammary tumor virus model of breast cancer resulted in the identification of an amplified region of DNA on human chromosome 11 band q13. This amplification occurs in approximately 15% of primary breast cancers. Several candidate oncogenes map within the amplicon but by analysing expression of these genes a strong case can be made for a role for cyclin D1 in tumorigenesis. Immunohistochemical staining indicates that cyclin D1 is expressed at elevated levels in around 40% of breast cancers, including those with the 11q13 amplification. The potential function of cyclin D1 as a regulator of early cell division cycle events would be consistent with a role in neoplasia.

• MeSH
• amplifikace genu MeSH
• cyklin D1 MeSH
• cykliny fyziologie   MeSH
• lidé MeSH
• lidské chromozomy, pár 11 genetika   MeSH
• nádory prsu genetika   MeSH
• onkogenní proteiny fyziologie   MeSH
• Southernův blotting MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Immunohistochemical staining with a monoclonal antibody against human cyclin D1 can be used to identify breast cancers that have an amplification of the q13 region of chromosome 11. In general, the intensity of staining is directly proportional to the degree of DNA amplification. In two unusual tumors, in which the CCND1 locus is highly amplified but staining is relatively weak, it appears that the DNA has undergone rearrangement and that the amplified/rearranged CCND1 allele may have reduced transcriptional activity. More significantly, the immunohistochemical technique identifies additional tumors in which the cyclin D1 gene is overexpressed with only marginal or undetectable increases in copy number, implying that other mechanisms can lead to deregulated expression. These results suggest that the frequency of overexpression is much higher than previously concluded from DNA-based analyses and that more than one-third of human breast cancers may contain excessive levels of cyclin D1. The technique we describe should facilitate the detection of this abnormality in a clinical setting and clarify its prognostic significance.

• MeSH
• alely MeSH
• amplifikace genu * MeSH
• cyklin D1 MeSH
• cykliny analýza   biosyntéza   genetika   MeSH
• DNA nádorová analýza   metabolismus   MeSH
• exprese genu MeSH
• genetická transkripce MeSH
• imunohistochemie MeSH
• lidé MeSH
• lidské chromozomy, pár 11 * MeSH
• mapování chromozomů MeSH
• monoklonální protilátky MeSH
• nádorové buňky kultivované MeSH
• nádory prsu metabolismus   patologie   MeSH
• onkogenní proteiny analýza   biosyntéza   genetika   MeSH
• prognóza MeSH
• RNA nádorová analýza   biosyntéza   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

In an attempt to obtain cell lines from the different components found in primary breast cancers, we used a low-calcium medium to culture epithelial cells of mixed phenotype and a recombinant T antigen containing retrovirus to immortalize cells found in these cultures. In each case, the histology of the sample used for culture was examined in detail and the best growth was obtained from samples associated with a substantial in situ or benign component and from lobular rather than ductal carcinomas. Clonal cell lines were developed from each of 4 tumours: 1 infiltrating ductal (tumour number 2), 2 infiltrating lobular (tumours 3 and 5) and 1 mucoid (tumour 6). To try to identify the phenotype and origin of the cell lines, immunohistochemical markers, histological analysis of tissue sections and behavioural markers were used. All the cell lines expressed mainly luminal epithelial cell markers, but the basal epithelial keratin, keratin 14, was also expressed homogeneously or heterogeneously. Growth in agar was seen with some but not all cell lines derived from only 1 tumour (tumour 5) and tumour development in nude mice was observed (with low efficiency) with cell lines from only 1 tumour (tumour 6). The data suggest that the cell lines obtained from the infiltrating ductal carcinoma (tumour 2) developed from cells cultured from the associated benign component, while the cell lines from tumours 3, 5 and 6 may each have developed from a cell in an early stage of malignancy. When tested for their ability to undergo morphogenesis on extracellular matrix components, cell lines from tumour 2 made well-developed ductal-alveolar-like structures, while those from the other tumours did not.

• MeSH
• buněčná diferenciace MeSH
• buněčné klony MeSH
• gely MeSH
• genetické vektory MeSH
• imunohistochemie MeSH
• intraduktální neinfiltrující karcinom chemie   patologie   MeSH
• keratiny analýza   MeSH
• lidé MeSH
• muciny analýza   MeSH
• myši nahé MeSH
• myši MeSH
• nádorový supresorový protein p53 analýza   MeSH
• nádory prsu chemie   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH