Disease relevance of Genes, Retinoblastoma

• The retinoblastoma susceptibility gene (RB) product, the retinoblastoma protein (pRb), functions as a regulator of cell proliferation [1].
• To determine whether the retinoblastoma gene (Rb) localized at 13q14, might be the target of recessive mutations in lung cancer, eight primary SCLC tumors and 50 cell lines representing all major histologic types of lung cancer were examined with the Rb complementary DNA probe [2].
• Structural abnormalities within the Rb gene were observed in 1/8 (13%) primary SCLC tumors, 4/22 (18%) SCLC lines, and 1/4 (25%) pulmonary carcinoid lines (comparable to the 20 to 40% observed in retinoblastoma), but were not detected in other major types of lung cancer [2].
• The retinoblastoma-susceptibility (RB) gene, a prototype of tumor suppressor genes, has recently been associated with development and/or progression of bladder cancer, as well as sarcoma and small-cell lung cancer [3].
• We have studied the initial effects of adenovirus E1A expression on the retinoblastoma (RB) gene product in normal quiescent cells [4].

High impact information on Genes, Retinoblastoma

• The retinoblastoma (RB) gene is one of the most extensively studied tumour-suppressor genes [5].
• This 105 kd E1A-binding protein cross-reacts with two different antibodies against the retinoblastoma (RB) gene product [6].
• A gene encoding a messenger RNA (mRNA) of 4.6 kilobases (kb), located in the proximity of esterase D, was identified as the retinoblastoma susceptibility (RB) gene on the basis of chromosomal location, homozygous deletion, and tumor-specific alterations in expression [7].
• Our results are consistent with the model that autocrine production of TGF-beta negatively regulates the cycling status of early hematopoietic progenitors through interaction with the Rb gene product [8].
• The protein product of the retinoblastoma (RB) gene is thought to function in a pathway that restricts cell proliferation [9].

Chemical compound and disease context of Genes, Retinoblastoma

• The expression of the retinoblastoma susceptibility (RB) gene was investigated in P19 embryonal carcinoma cells and in these cells induced to differentiate with retinoic acid (RA) or with dimethyl sulfoxide (DMSO) [10].
• Gossypol plasma levels were measured (n = 8) and the modulation of the retinoblastoma (Rb) gene protein and Cyclin D1 was assessed by serial biopsies (n = 4) [11].
• Alterations in genes involved in regulating the cell cycle such as cyclin D1 and the retinoblastoma (Rb) gene have also been shown to influence cellular response to MTX [12].

Biological context of Genes, Retinoblastoma

• Extensive apoptosis occurs in the nervous system of mouse embryos homozygous mutant for a targeted disruption of the retinoblastoma (Rb) gene [13].
• Expression of cyclin D1, but not of cyclins A and E, is induced by transfection of the Rb gene into Rb-deficient tumor cells [14].
• Cotransfection of a reporter gene under the control of the D1 promoter, together with the Rb gene, into Rb-deficient cell lines demonstrates stimulation of the D1 promoter by Rb, which parallels the stimulation of endogenous cyclin D1 gene expression [14].
• Dinucleotide repeat polymorphism at the human PDGF RB gene [15].
• There were no other significant correlations with p53 point mutation or loss of heterozygosity in chromosomes 5q, 17p, and 18q and Rb gene, which have been suggested to be involved in the progression of CRC of both morphological types [16].

Anatomical context of Genes, Retinoblastoma

• Homologous recombination at the retinoblastoma susceptibility gene (Rb) in embryonic stem cells derived from mouse strain 129 was 20-fold more efficient with a 129-derived targeting construct than with a BALB/c-derived construct [17].
• Fibroblasts derived from embryos homozygous for a disruption of the retinoblastoma gene (Rb) exhibit a shorter G1 than their wild-type counterparts, apparently due to highly elevated levels of cyclin E protein and deregulated cyclin-dependent kinase 2 (CDK2) activity [18].
• From the clinical point of view, loss of Rb gene was associated with a poor performance status; low hemoglobin levels; high creatinine, C-reactive protein, and lactic dehydrogenase serum levels; high percentage of bone marrow plasma cells (BMPC); extensive bone lytic lesions; and advanced clinical stage [19].
• Here we examine the role of the retinoblastoma gene (Rb) in myocyte survival [20].
• Human ovarian surface epithelial cells and esophageal epithelial cells were immortalized by the expression of HPV16 E6 and E7, which drive cells to proliferate by inactivating p53 and Rb genes [21].

Associations of Genes, Retinoblastoma with chemical compounds

• Sequence analysis of the entire coding region of the Rb gene revealed point mutations (AAC to GAC) resulting in codon 123 (Asn to Asp) changes in the Caov-4 cell line [22].
• Structural alterations in the entire coding region (exons 1 to 27) of the Rb gene in methylene-chloride-induced medaka liver tumors were investigated using polymerase chain reaction and single strand conformation polymorphism analysis [23].
• Abnormalities in the Rb gene may also have profound effects on MTX sensitivity [12].
• A particularly efficient model of prostatic carcinogenesis in mice involves T + E2 treatment of mice bearing grafts of wild-type rat urogenital mesenchyme (rUGM) plus retinoblastoma gene (Rb) knockout (Rb-KO) prostatic epithelium (rUGM + Rb-KO-PRE) [24].

Gene context of Genes, Retinoblastoma

• In both LS513 and LS1034, WAF1 induction correlated with reduced cyclin E-associated kinase activity in vitro and suppression of the retinoblastoma susceptibility gene (Rb) protein phosphorylation in vivo [25].
• Notably, alterations of one of the CDKIs, p53 and Rb genes appear to obviate the need for inactivation of other genes in the same pathway [26].
• Our previous and these results suggested that the expression level of MDM2 protein is independent of the status of the p14ARF, p53, Rb genes [27].
• These results demonstrate that OxLDL or its lipid peroxidation products, by generation of an oxidative stress, enhances the expression of p21 and Rb genes, leading to an accumulation of the Hypo-P active form of the tumor suppressor Rb [28].
• In full-term placenta c-myc expression was undetectable while Rb gene product and PCNA immunoreactivity declined markedly [29].

Analytical, diagnostic and therapeutic context of Genes, Retinoblastoma

• Therefore, we investigated bcl-2, p53, and retinoblastoma gene (Rb) expression immunohistochemically; the occurrence of bcl-2, c-myc, and Rb gene rearrangements using Southern blotting; and the presence of ras and p53 gene somatic mutations by single-strand conformation polymorphism assay in a panel of 18 well-characterized ALCLs [30].
• Immunohistochemistry of the RB protein proved to be the most sensitive method for the detection of Rb gene inactivation [31].
• Germline mutation in the retinoblastoma (RB) gene leads to tumor formation in both human and experimental animal models, and reintroduction of wild-type RB is able to suppress neoplastic phenotypes [32].
• Counterflow centrifugal elutriation and immunoblotting techniques were used to study the expression of the retinoblastoma (RB) gene during the cell cycle of BV173 chronic myeloid leukemia (CML) cells [33].
• Using a Syrian hamster cDNA probe homologous to the human retinoblastoma gene (RB), we have localized the gene to chromosome band 15q13 by conventional in situ hybridization [34].

References