Defects in the mechanisms controlling the cell cycle are crucial in cell transformation and/or tumour progression. p21 WAF1/CIP1 is an inhibitor of cyclin-dependent kinases, induced by p53-dependent and p53-independent pathways, which can block progression through the cell cycle. p21 WAF1/CIP1 expre
Cyclin-d1-gene amplification and expression in breast carcinoma: Relation with clinicopathologic characteristics and with retinoblastoma gene product, p53 and p21waf1 immunohistochemical expression
β Scribed by Mattia Barbareschi; Paola Pelosio; Orazio Caffo; Fiamma Buttitta; Silvia Pellegrini; Renzo Barbazza; Paolo Dalla Palma; Generoso Bevilacqua; Antonio Marchetti
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- French
- Weight
- 162 KB
- Volume
- 74
- Category
- Article
- ISSN
- 0020-7136
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β¦ Synopsis
Cyclin D1 is a major positive regulator of the G 1 restriction point promoting inactivation of the retinoblastoma protein (RB). The cyclin D1 gene is rearranged, amplified and/or over-expressed in several human neoplasms. In the present series of 64 human breast carcinomas, cyclin D1 amplification (4-to 8-fold) was seen in 24% of cases, and cyclin-D1 immunohistochemical over-expression was seen in 50% of cases. Amplification and over-expression were statistically associated; however, divergent result were seen in 30% of cases. Some of these discrepancies may reflect the fact that cyclin-D1 expression may be due to mechanisms other than gene amplification. Cyclin-D1 over-expression, but not cyclin-D1 amplification, was associated with positive oestrogen-receptor immunoreactivity. Cyclin-D1 amplification was associated with high RB expression, and 4 cases (7%) with absent RB immunoreactivity showed no cyclin-D1 amplification nor expression. Our data support the hypothesis that cyclin-D1 amplification may be associated with enhanced gene transcription and with high RB expression, that high ER expression may cooperate in maintaining high levels of cyclin-D1 protein, and that loss of RB function, as assessed by the lack of RB immunoreactivity, may be related to normal cyclin-D1 gene copy number and low cyclin-D1 expression. Int.
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