Mutant p53 gain of function in human osteosarcoma 3AB-OS cancer stem cells

Cellule staminali di osteosarcoma umano 3AB-OS: un modello per analizzare le proprietà oncogeniche di p53 mutata.

Alterazioni del gene TP53 si riscontrano in circa il 50% dei tumori umani (1). Negli ultimi anni è stato dimostrato che la proteina mutata p53 (mp53) acquisisce nuove proprietà oncogeniche, definite “gain of function” (GOF), che contribuiscono alla progressione tumorale (2). In questo studio è stato analizzato lo stato del gene TP53, della proteina da esso espressa e il loro ruolo nella promozione della proliferazione, invasività, resistenza all’apoptosi e staminalità delle cellule 3AB-OS, una linea tumorale staminale precedentemente isolata dalle cellule di osteosarcoma umano MG63 (3). Analisi comparative di RT-PCR, Methylation-Specific-PCR (MSP), Fluorescent-in situ-hybridization (FISH) e…

Retinoblastoma: History of His Identification, Characterization and Treatment

The first description of a tumor resembling retinoblastoma (RB) was provided on 1597 by Pieter Pauw, who described a malignancy invading the orbit, the temporal region, and the cranium, filled with a "substance similar to brain tissue mixed with thick blood and like crushed stone". Since then, a number of retinal tumors were described and named until the 1922 when Verhoeff called these tumors RB, a term that the American Ophthalmological Society adopted in 1926. In 1971 Knudson focused on RB, and proposed his ‘two-hit’ theory of the molecular etiology of RB. In 1986, the RB1 gene was identified and the ‘two-hit’ theory of Knudson was validated. Successively, new studies in developing retina…

Mutant p53 gain of function can be at the root of dedifferentiation of human osteosarcoma MG63 cells into 3AB-OS cancer stem cells

Osteosarcoma is a highly metastatic tumor affecting adolescents, for which there is no second-line chemotherapy. As suggested for most tumors, its capability to overgrow is probably driven by cancer stem cells (CSCs), and finding new targets to kill CSCs may be critical for improving patient survival. TP53 is the most frequently mutated tumor suppressor gene in cancers and mutant p53 protein (mutp53) can acquire gain of function (GOF) strongly contributing to malignancy. Studies thus far have not shown p53-GOF in osteosarcoma. Here, we investigated TP53 gene status/role in 3AB-OS cells-a highly aggressive CSC line previously selected from human osteosarcoma MG63 cells-to evaluate its involv…

A short story of 3AB-OS Cancer Stem Cells, a possible model for studying cancer stemness

All tumors contain a population of Cancer Stem Cells (CSCs) responsible for the initiation, growth and development of the tumor and a challenge in cancer research is their identification and eradication. In our laboratory, by chemical treatment of the human osteosarcoma MG63 cell line, we have isolated and characterized the human OS CSC line (3AB-OS). 3AB-OS CSCs have a significant chromosomal complexity and a large number of molecular abnormalities which appear to be strongly congruent with those described in a large number of pediatric and adult osteosarcomas. 3AB-OS cells transdifferentiated in vitro into cells of all three primary germ layers and, when xenografted in athymic mice they w…

Clivaggio e shuttling nucleo-citoplasmatico della proteina Sirt1, in cellule di carcinoma mammario MDA-MB231.

Sirt1 è una proteina nota per il suo ruolo di istone deacetilasi NAD+ dipendente che sembra essere coinvolta in una ampia gamma di processi cellulari, quali regolazione genica, controllo dello stato metabolico, meccanismi di sopravvivenza allo stress. Dalla letteratura emergono dati contrastanti concernenti la funzione di Sirt1 nei tumori, le vengono infatti attribuiti ruoli sia di oncogene che di soppressore tumorale, argomento fortemente dibattuto. A conferma di ciò, la localizzazione subcellulare e la funzione di Sirt1 variano nei differenti tipi cellulari (1). E’ anche noto che Sirt1 risulta frequentemente clivata in varie linee cellulari grazie ad attività proteolitiche nucleari (2). Q…

STUDY ON P53 GAIN OF FUNCTION IN 3AB-OS CANCER STEM CELLS