<i>p53</i> Mutations and Histologie Type of Invasive Breast Carcinoma

Marchetti, Antonio; Buttitta, Fiamma; Pellegrini, Silvia; Diella, Francesca; Campani, Daniela; Cecchetti, D; Squartini, F; Callahan, Robert; Bistocchi, M

doi:10.1111/j.1749-6632.1993.tb17196.x

Cited by 54 publications

(62 citation statements)

References 10 publications

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“…The inter-relations among hormonal control, p53 and angiogenesis activation could be explained by the presence in the VEGF promoter region (Zhang et al, 2000) either of a specific cis-element recognised by p53 or of a specific oestrogen-response element (Hyder et al, 2000). In addition, p53 protein, less frequently mutated in ILC than in IDC (Marchetti et al, 1993), is able to down-regulate the promoter activity of VEGF in a dose-dependent manner (Mukhopadhyay et al, 1995) and to inactivate the HIF-1a protein . Conversely, the higher incidence of p53+ IDC compared to ILC, associated with a higher VEGF concentration, is in keeping with a possible down-regulation of angiogenesis by p53 tumour suppressor gene function through a block of HIF-1 activity, with the formation of a stable complex wild-type p53/HIF-1a and the subsequent ubiquitination of HIF-1a.…”

Section: Discussionmentioning

confidence: 99%

Infiltrating ductal and lobular breast carcinomas are characterised by different interrelationships among markers related to angiogenesis and hormone dependence

et al. 2002

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To obtain a more integrated understanding of the different breast cancer phenotypes and to investigate whether biomolecular profiles can distinguish between specific histotypes, we explored the interrelations among several biologic variables indicative of, or related to, hormone dependence, proliferation and apoptosis control, and angiogenesis in ductal and lobular carcinomas, the most common histotypes. Oestrogen and progesterone receptors, tumour proliferative activity, the expression of cyclin A, p16 ink4A , p27 kip1 , p21 waf1 , p53, bcl-2, and levels of vascular endothelial growth factor and hypoxia-inducible factor1a (HIF-1a) were evaluated in 190 in ductal and 67 lobular carcinomas. Our findings support the hypothesis that in ductal and lobular carcinomas are two distinct, partially phenotypically unrelated entities, the latter being characterised by the presence of features indicative of differentiation such as oestrogen receptors, low proliferation and lack of p53 expression and associated with low vascular endothelial growth factor content compared to angiogenesis in ductal carcinomas. Conversely, no significant difference was found between lobular carcinomas and in ductal carcinomas considering the frequency distribution of PgRpositive cases, cyclin-dependent kinase inhibitors acting at the G1/S boundary, bcl-2 and HIF-1a protein expression. Although both generally defined as hormone responsive, in ductal and lobular carcinomas are also characterised by biologic patterns in which proteins related to hormone responsiveness, cell-cycle control, apoptosis and angiogenesis were differently associated. This finding suggests the need to refine breast cancer characterisation in order to provide detailed information about individual tumours, or subsets of tumours, that will help in defining optimal treatment approaches.

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Section: Discussionmentioning

confidence: 99%

Infiltrating ductal and lobular breast carcinomas are characterised by different interrelationships among markers related to angiogenesis and hormone dependence

et al. 2002

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“…The sum of the percentages for each group is greater than 100%, since some tumors showed activations of more than one gene. The disparity in Wnt1 activation frequencies between the two nontransgenic groups (Chi square test; P50.001) is most likely due to the di erences in the genetic backgrounds (Marchetti et al, 1991). Proviral insertions were not detected in the *36 kb region containing the Fgf8 gene in tumors from the nontransgenic littermate group that showed Fgf8 expression (data not shown), suggesting long distance activation by MMTV in these tumors.…”

Section: Activation Ofmentioning

confidence: 95%

Preferential activation of Fgf8 by proviral insertion in mammary tumors of Wnt1 transgenic mice

Kapoun

Shackleford

1997

Oncogene

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Mouse mammary tumor virus (MMTV) is an insertional mutagen that has been demonstrated to transcriptionally activate¯anking cellular proto-oncogenes. Previously we have used MMTV infection to accelerate mammary tumorigenesis in Wnt1 transgenic mice in order to identify genes that cooperate with the Wnt1 oncogene. Initial investigations into the resulting tumor collection, screened primarily by Southern analysis, showed that three ®broblast growth factor genes, Fgf8, Fgf3 and Fgf4, sustain activating insertion mutations in 10%, 42% and 6% of the tumors, respectively. Here, in an examination of the tumors from MMTV-infected Wnt1 transgenic mice that emphasizes Northern analysis, we report transcriptional activation of Fgf8 in 30 additional tumors (increasing the percentage of activations to 50%), while no signi®cant changes in the activation frequency of Fgf3 or Fgf4 were found. To determine the frequency of insertional activation in normal mice, we examined tumors from MMTV-infected nontransgenic littermates of the Wnt1 transgenics and from MMTVinfected BALB/c mice. Fgf8, Fgf3 and Fgf4 were found to be activated in 11%, 80% and 5%, respectively, of the tumors in the combined nontransgenic groups. Thus, there appears to be an increased predisposition for Fgf8 activations in Wnt1 transgenic mice versus normal mice, suggesting that cells expressing Wnt1 are especially sensitized to stimulation by FGF8 compared with FGF3 or FGF4. In contrast, the activation frequency of Fgf3 in tumors from MMTV-infected Wnt1 transgenic mice was approximately one-half that of normal mice. Our results show that this in vivo model of multistep tumorigenesis reveals signi®cant di erences in the activation rates of Fgf3 and Fgf8 depending upon the status of Wnt1 expression in the mammary gland. The di erential activation of these Fgfs may relate to di erences in their signaling pathways.

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“…Genetic analysis of the role of the Drosophila Wingless (Wg) and Notch signaling pathways has provided evidence that they both function in many of the same patterning events during development and that their expression has a`yin ± yang' type of in¯uence Marchetti et al (1991), Peters (1990) and our unpublished data on these events (reviewed in Axelrod et al, 1996). Genetic analysis of Drosophila has identi®ed several genes comprising the Wg signaling pathway (reviewed in Dierick, et al, 1999).…”

Section: Biological Consequences Of Target Gene Expression On Mammarymentioning

confidence: 99%

“…If Sell and Pierce (1994) were correct in their conclusion that hyperplasias were the result of mutated stem cells, normal mammary epithelial stem cells in CzechII mice might become infected by MMTV and acquire mutations. If stem cells produce all the cells in a mammary gland then normal mammary outgrowths from implanted (Marchetti et al, 1991) probes, respectively at 658C using previously described conditions (Gallahan and Callahan, 1987a) fragments might be clonal populations from a single stem cell. To test this hypothesis, Kordon and Smith (1998) transplanted mammary epithelial fragments, chosen randomly, from mature, parous MMTV (CzechII)-infected female mice into gland-free mammary fat-pads of syngeneic mice.…”

Section: The Mmtv Infectious Pathwaymentioning

confidence: 99%

“…The frequency with which the common integration sites for MMTV are rearranged by the virus in mammary tumors seems to be dependent on the host mouse strain and the strain of virus (Table 1) (Marchetti et al, 1991;Peters, 1990). For instance, Wnt1 is activated by MMTV in 75% of the C3H mammary tumors whereas in mammary tumors of other mouse strains infected with MMTV(C3H) or other strains of MMTV the frequency of Wnt1 activation is 26 ± 40%.…”

Section: Biological Consequences Of Target Gene Expression On Mammarymentioning

confidence: 99%

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MMTV-induced mammary tumorigenesis: gene discovery, progression to malignancy and cellular pathways

2000

Self Cite

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The study of the mouse mammary tumor virus (MMTV) has provided important insights into the mechanisms of gene transcription regulation by steroid hormones, the mode of action of heritable super antigens and the progressive nature of neoplastic transformation in the mammary gland. Here we describe the current situation with respect to the latter aspect of MMTV biology and the prospects for further advance in our understanding of breast cancer in humans that may be expected from a continued study of MMTV-induced mammary neoplasia. MMTV is a heritable somatic mutagen whose target range is limited. Commonly, the tumorigenic capacity of MMTV is restricted to mammary gland, whereas infection is found in a variety of cell types. In order to replicate, proviral DNA must be inserted into the cell DNA and cell division is required to ®x the mutation. Yet only in the mammary epithelium does this lead to neoplastic transformation. This suggests a unique relationship between MMTV and mammary epithelium. In evaluating this relationship, we and others have discovered genes and potential gene pathways that are pertinent in mammary di erentiation and neoplasia. In addition, the clonal nature of these progressive events from normal to malignant phenotype has become increasingly clear. The weight of these observations compel us to conclude that mammary neoplasms arise from multipotent mammary epithelial cells through a process of acquired mutations that are re¯ected in the increasingly malignant nature of the population of progeny produced by these damaged stem cells.

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p53 Mutations and Histologie Type of Invasive Breast Carcinoma

Cited by 54 publications

References 10 publications

Infiltrating ductal and lobular breast carcinomas are characterised by different interrelationships among markers related to angiogenesis and hormone dependence

Infiltrating ductal and lobular breast carcinomas are characterised by different interrelationships among markers related to angiogenesis and hormone dependence

Preferential activation of Fgf8 by proviral insertion in mammary tumors of Wnt1 transgenic mice

MMTV-induced mammary tumorigenesis: gene discovery, progression to malignancy and cellular pathways

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