mdm2 gene alterations and mdm2 protein expression in breast carcinomas

Abstract

This study investigates the mdm2 gene status and expression in 66 surgically resected human breast carcinomas, with correlations with clinico-pathological and biological data (histological type, grading, steroid receptor status, p53 expression, proliferative activity). Four (7.7 per cent) out of 52 informative cases bear mdm2 gene amplification (four-to ten-fold) and 8 (15.4 per cent) of 52 cases showed borderline amplification (three-fold). Nine (13.6 per cent) out of 66 cases showed strong mdm2 nuclear immunoreactivity. Twenty-seven (40.9 per cent) cases showed isolated mdm2 reactive nuclei. All cases with clear amplification showed a high percentage of mdm2 immunoreactive nuclei. The relationship between gene amplification and mdm2 protein expression is highly significant (P < 0.0001). No association was observed between mdm2 gene amplification and any of the considered clinico-pathological and biological parameters, while mdm2 immunoreactivity showed a significant association only with oestrogen receptor immunoreactivity (P = 0.009). p53 expression was associated neither with mdm2 gene amplification nor with mdm2 immunoreactivity. It could be tempting to hypothesize that the evaluation of the combined mdm2/p53 immunohistochemical phenotype in human breast carcinoma could give us better prognostic information than the evaluation of the expression of the p53 protein alone.

MEK-ERK Signaling Controls Hdm2 Oncoprotein Expression by Regulating hdm2 mRNA Export to the Cytoplasm

“…In the specific case of breast cancer, which may well be a suitable target for such interventions, we have previously demonstrated that elevated levels of Hdm2 protein in proliferating cultures of breast cancer cell lines with ER␣ ϩve , compared with ER␣ Ϫve , phenotypes, correlates with transcription from the P2 promoter of the hdm2 gene in the ER␣ ϩve cells (37). In breast tumor samples, Hdm2 protein is overexpressed compared with normal cells in as many as 50% of cases (34 -36); however, in most cases in which Hdm2 expression is observed in breast cancer, it is limited to small patches of cells in the tumor (34). Additionally, one study determined that, of the tumors in which hdm2 mRNA was up-regulated, only 69% showed Hdm2 protein overexpression (35).…”

A single nucleotide polymorphism in the p53 pathway interacts with gender, environmental stresses and tumor genetics to influence cancer in humans

“…Over 10 years ago, it was first noted that MDM2 mRNA and protein levels are heightened in breast tumors that express the estrogen receptor (ER), a critical component of the estrogen signaling pathway (Sheikh et al, 1993;Gudas et al, 1995;Marchetti et al, 1995;Okumura et al, 2002). Subsequently, the expression of ER-a was shown to induce transcription of MDM2.…”

Genetic alterations on chromosome 16 and 17 are important features of ductal carcinoma in situ of the breast and are associated with histologic type

“…From this clone a 400 bp I/I fragment of exon II was used for hybridization. The MDM2 probe was a 585 bp reverse transcription PCR (RT-PCR) fragment spanning nucleotides 650-1214 of the published cDNA sequence (Oliner et al, 1992;Marchetti et al, 1995). The  and  probes were kindly provided by Dr Theillet (Adnane et al, 1991).…”