Without internal affiliation

  • Author: Rohde, M.

    Danish Cancer Society, Division of Tumor Biology

  • Author: Warthoe, P.

    Danish Cancer Society, Division of Tumor Biology

  • Author: Gjetting, Torben

    Unknown

  • Author: Lukas, J.

    Danish Cancer Society, Division of Tumor Biology

  • Author: Bartek, J.

    Danish Cancer Society, Division of Tumor Biology

  • Author: Strauss, M.

    Danish Cancer Society, Division of Tumor Biology

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The product of the retinoblastoma susceptibility gene, pRb, is a negative regulator of cell growth. It functions by regulating the activity of transcription factors. Rb represses some genes by sequestering or inactivating the positive transcription factor E2F and seems to activate some others by interacting with factors like Spl or ATF-2, However, there are only a few examples of genes which are positively regulated by pRb. In order to find out if there are common mechanisms for promoter regulation by pRb, we were interested to identify more genes which are either stimulated or repressed by pRb, Using the method of differential display (DDRT-PCR) in combination with nuclear run-on analyses we were able to detect a number of genes which are upregulated by ectopic expression of the Rb gene in Rb-deficient mammary carcinoma cells, We could demonstrate not only stimulation of the endogenous mutant Rb gene but also positive regulation of genes coding for diverse classes of proteins, including the endothelial growth and the proteoglycans versican and PG40, As a second approach, we investigated gene expression in cell lines established from Rb deficient heterozygous and homozygous knockout mouse embryos and normal mice, We have identified several genes the expression of which correlates positively or negatively with the presence of Rb. These data provide further evidence for pRb being a master regulator of a complex network of gene activities defining the difference between dividing and resting or differentiated cells.
Keyword: retinoblastoma protein,thrombospondin,DDRT-PCR,differential display,endothelin,gene regulation
Original languageEnglish
JournalOncogene
Publication date1996
Volume12
Issue11
Pages2393-2401
ISSN0950-9232
StatePublished
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