Loss of retinoblastoma tumor suppressor protein makes human breast cancer cells more sensitive to anti-metabolite exposure. (Articolo in rivista)

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  • Loss of retinoblastoma tumor suppressor protein makes human breast cancer cells more sensitive to anti-metabolite exposure. (Articolo in rivista) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1158/1078-0432.CCR-07-2065 (literal)
Alternative label
  • Derenzini M, Donati G, Mazzini G, Montanaro L, Vici M, Ceccarelli C, Santini D, Taffurelli M, Trere' D. (2008)
    Loss of retinoblastoma tumor suppressor protein makes human breast cancer cells more sensitive to anti-metabolite exposure.
    in Clinical cancer research (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Derenzini M, Donati G, Mazzini G, Montanaro L, Vici M, Ceccarelli C, Santini D, Taffurelli M, Trere' D. (literal)
Pagina inizio
  • 2199 (literal)
Pagina fine
  • 2209 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 14 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 7 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Department of Experimental Pathology, Unit of Clinical Pathology,University of Bologna, Italy; Institute of Molecular Genetics,Histochemisty and Cytochemistry, CNR – Pavia, Italy; Department of Surgical Pathology, University of Bologna, Italy; Department of Surgery, University of Bologna, Italy. (literal)
Titolo
  • Loss of retinoblastoma tumor suppressor protein makes human breast cancer cells more sensitive to anti-metabolite exposure. (literal)
Abstract
  • Purpose: The RB tumor-suppressor activity may influence the therapeutic response in human breast cancers. The effect of adjuvant therapy on clinical outcome of breast cancer patients was analyzed and the sensitivity to 5-Fluorouracil and Methotrexate investigated in MCF-7 breast cancer cells, according to their RB status. Experimental Design: RB protein (pRB) expression was prospectively evaluated by immuno-cytochemistry in 518 consecutive patients and its predictive value determined according to the adjuvant therapeutic treatments. MCF-7 breast cancer cells silenced for RB1 expression, were treated with 5-Fluorouracil and Methotrexate, at the same concentrations and time exposures as determined in the interstitium of breast cancers of patients treated with adjuvant chemotherapy. Results: Standard systemic chemotherapy (Cyclophosphamide, Methotrexate and 5-Fluorouracil) greatly improved the clinical outcome of patients whose cancer lacked pRB but not of patients either expressing pRB or with inactivated, hyper-phosphorylated pRB. Absence of pRB was associated with a worse prognosis in patients treated with endocrine therapy alone. 5-Fluorouracil and Methotrexate significantly reduced the growth rate of RB1-silenced but not of control MCF-7 cells. This was likely due to the absence of a DNA damage checkpoint in RB1-silenced but not in control cells, with accumulation of DNA double strand breaks in RB1-silenced but not in control cells. Conclusions: The absence of pRB expression renders human breast cancer cells more sensitive to 5-FU and MTX and predicts a good clinical outcome for patients treated with adjuvant chemotherapy. We suggest that patients with RB-negative breast cancers should be treated by systemic chemotherapy. (literal)
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