pRb2/p130: a new candidate for retinoblastoma tumor formation

Falco, Giulia De; Giordano, Antonio

doi:10.1038/sj.onc.1209614

Cited by 23 publications

(19 citation statements)

References 82 publications

(93 reference statements)

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“…The promoter region contains binding motifs for transcription factors Sp1 and ATF, but no TATA or CAAT elements. The RB1 polypeptide is a 110-kDa phosphoprotein (pRb or pRB) that shares homology with two other paralogues, pRB2/p130 and p107, comprising the Rb family of proteins [1]. They share some functional domains and have overlapping roles in regulating growth control during development [2].…”

Section: Structure and Function Of Rb1mentioning

confidence: 99%

RETRACTED ARTICLE: Molecular biology of retinoblastoma

Álvarez

2008

Clin Transl Oncol

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Retinoblastoma (Rb), the most common intraocular tumor in childhood, is caused by the loss of function of both retinoblastoma susceptibility gene (RB1 or Rb1) alleles. In 1971, Alfred Knudson proposed his "two-hit" theory based upon empiric observations of the clinical genetics of Rb, revealing the role of tumor-suppressor genes in human cancer. Knudson proposed that: "In the dominant inherited form of Rb, one mutation is inherited via germ line and the second occurs in somatic cells. In the nonhereditary form, both mutations occur in somatic cells." The Knudson hypothesis was validated later with the cloning of RB1, the first tumor-suppressor gene to be identified. A few years later, Harbour extended these findings to small-cell lung cancer, showing that the RB1 locus was disrupted in tumors other than Rb and osteosarcoma. Since then, it has been found that most, if not all, tumors have defects in their RB1 pathway through genetic lesions in the RB1 gene itself or other genes in the pathway. The history of Rb research highlights how basic research on a rare childhood cancer can have a much broader effect on a disease that affects millions of people each year worldwide.

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Section: Structure and Function Of Rb1mentioning

confidence: 99%

RETRACTED ARTICLE: Molecular biology of retinoblastoma

Álvarez

2008

Clin Transl Oncol

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“…Thus, the A/B pocket is likely to play an important role in RB tumor suppressor functions [5,6] . The A/B and C domains are conserved in 2 other Rb gene family proteins, p107 and p130, which also bind to LXCXE and regulate cell cycle-dependent transcription [10] . The activities of p107 and p130 overlap with, but are not identical to RB, and these proteins may partially substitute for RB functions.…”

Section: Introductionmentioning

confidence: 99%

Growth suppression and radiosensitivity increase by HMGB1 in breast cancer

Jiao

Wang

Fan

2007

Acta Pharmacologica Sinica

100

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Aim: HMGB1 (high-mobility group box-1) is a nuclear protein containing a consensus RB (retinoblastoma)-binding LXCXE motif. In this study, we studied the potential association of HMGB1 and RB and the in vitro and in vivo activities of HMGB1 in human breast cancer cells. Methods: The protein-protein interaction was determined by immunoprecipitation-Western blotting and glutathione-S-transferase capture assays; cell growth and radiosensitivity were examined by cell counts, MTT assay, and clonogenic assay; cell cycle progression and apoptosis were evaluated using flow cytometry; and the antitumor activity of HMGB1 was examined with tumor xenografts in nude mice. Results: HMGB1 was associated with RB via a LXCXE motif-dependent mechanism. HMGB1 enhanced the ability of RB for E2F and cyclin A transcription repression. The increased expression of HMGB1 conferred an altered phenotypes characterized by the suppression of cell growth; G 1 arrest and apoptosis was induced in MCF-7 cells containing the wildtype retinoblastoma (Rb) gene, but showed no activities in BT-549 cells containing the Rb gene deletion. The HMGB1-induced apoptosis accompanied by caspase 3 activation and PARP (poly(ADP-ribose)polymerase) cleavage. HMGB1 elevated the radiosensitivity of breast cancer cells in both the MCF-7 and BT-549 cell lines. The enhanced expression of HMGB1 caused a suppression of growth of MCF-7 tumor xenografts in nude mice, while LXCXE-defective HMGB1 completely lost antitumor growth activity. Conclusion: HMGB1 functions as a tumor suppressor and radiosensitizer in breast cancer. A HMGB1-RB interaction is critical for the HMGB1-mediated transcriptional repression, cell growth inhibition, G 1 cell cycle arrest, apoptosis induction, and tumor growth suppression, but is not required for radiosensitization. Therefore, it may be possible to design new therapies for the treatment of breast cancer that exert their effects by modulating the HMGB1 and RB regulatory pathway and HMGB1-related gene therapy.

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“…Proteins of the pRB family regulate transcription and progression of the cell cycle (34). P130 may operate as a tumor suppressor in small-cell lung carcinoma (35).…”

Section: Discussionmentioning

confidence: 99%

Identification of candidate biomarkers using the Experion™ automated electrophoresis system in serum samples from ovarian cancer patients

Kim

Park

et al. 2013

International Journal of Oncology

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Abstract. Ovarian cancer is the most common cause of diseaserelated death in women globally. Detection of ovarian cancer using new biomarkers is necessary for early diagnosis. To date, there have been no obvious biomarkers for ovarian cancer detection in the incipient stage. In this study, we discovered potential diagnostic serological biomarkers for ovarian cancer using the Experion™ automated electrophoresis system. Sera from 14 healthy women and 84 ovarian cancer patients at stages I-IV were applied to the Experion to compare the protein expression levels. To examine the protein expression pattern of Experion data, proteins in the samples were resolved using 10 and 15% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and visualized by silver staining. The candidate biomarkers elevated in ovarian cancer were purified and determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. α-2-macroglobulin (173.7 kDa), ceruloplasmin (147 kDa), inter-α-trypsin inhibitor family heavy chain-related protein (126 kDa), C-1 inhibitor (115.2 kDa) and hemoglobin α/β (14.4 kDa were overexpressed in the ovarian cancer sera. This study documents a novel way to measure ovarian cancer or cancer-related proteins for biomarkers using the Experion assay system, which should be easily adaptable for high-throughput diagnosis to establish databases of ovarian cancer for clinical applications.

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pRb2/p130: a new candidate for retinoblastoma tumor formation

Cited by 23 publications

References 82 publications

RETRACTED ARTICLE: Molecular biology of retinoblastoma

RETRACTED ARTICLE: Molecular biology of retinoblastoma

Growth suppression and radiosensitivity increase by HMGB1 in breast cancer

Identification of candidate biomarkers using the Experion™ automated electrophoresis system in serum samples from ovarian cancer patients

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