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Corrado D'Arrigo

Publications and source records attributed to Corrado D'Arrigo.

10 recordsLinked to original sources
PubMed2005

Expression of the Brn-3b transcription factor correlates with expression of HSP-27 in breast cancer biopsies and is required for maximal activation of the HSP-27 promoter.

In breast cancer, overexpression of the small heat shock protein, HSP-27, is associated with increased anchorage-independent growth, increased invasiveness, and resistance to chemotherapeutic drugs and is associated with poor prognosis and reduced disease-free survival. Therefore, factors that increase the expression of HSP-27 in breast cancer are likely to affect the prognosis and outcome of treatment. In this study, we show a strong correlation between elevated levels of the Brn-3b POU transcription factor and high levels of HSP-27 protein in manipulated MCF-7 breast cancer cells as well as in human breast biopsies. Conversely, HSP-27 is decreased on loss of Brn-3b. In cotransfection assays, Brn-3b can strongly transactivate the HSP-27 promoter, supporting a role for direct regulation of HSP-27 expression. Brn-3b also cooperates with the estrogen receptor (ER) to facilitate maximal stimulation of the HSP-27 promoter, with significantly enhanced activity of this promoter observed on coexpression of Brn-3b and ER compared with either alone. RNA interference and site-directed mutagenesis support the requirement for the Brn-3b binding site on the HSP-27 promoter, which facilitates maximal transactivation either alone or on interaction with the ER. Chromatin immunoprecipitation provides evidence for association of Brn-3b with the HSP-27 promoter in the intact cell. Thus, Brn-3b can, directly and indirectly (via interaction with the ER), activate HSP-27 expression, and this may represent one mechanism by which Brn-3b mediates its effects in breast cancer cells.

Base Sequence↗
PubMed2005

CUTL1 is a target of TGF(beta) signaling that enhances cancer cell motility and invasiveness.

CUTL1, also known as CDP, Cut, or Cux-1, is a homeodomain transcriptional regulator known to be involved in development and cell cycle progression. Here we report that CUTL1 activity is associated with increased migration and invasiveness in numerous tumor cell lines, both in vitro and in vivo. Furthermore, we identify CUTL1 as a transcriptional target of transforming growth factor beta and a mediator of its promigratory effects. CUTL1 activates a transcriptional program regulating genes involved in cell motility, invasion, and extracellular matrix composition. CUTL1 expression is significantly increased in high-grade carcinomas and is inversely correlated with survival in breast cancer. This suggests that CUTL1 plays a central role in coordinating a gene expression program associated with cell motility and tumor progression.

Animals↗
PubMed2004

Human murine mammary tumour virus-like agents are genetically distinct from endogenous retroviruses and are not detectable in breast cancer cell lines or biopsies.

It has been reported that a human murine mammary tumour virus (MMTV)-like virus (HMLV), which may be an endogenous human retrovirus (HERV), occurs in the human breast cancer cell lines T47D and MCF-7 and, in 38% of human breast cancer biopsies. As the aetiology of most breast cancers remains unknown, it is important to verify these observations in differing breast cancer populations worldwide. Thus, we sought to determine the genetic relationships between HMLVs, MMTVs, and HERVs, and to investigate the association between HMLVs and breast cancer biopsies from South London, UK. Phylogenetic analyses of the env/pol region indicated that HMLVs are indistinct from MMTVs, and that MMTVS/HMLVs exhibit only low sequence homologies with HERVs. A search of the human genome confirmed that HMLVs are not endogenous. Using MMTV polymerase chain reaction (PCR) primers described previously, we amplified DNA from all cell lines except MCF-7 and from 7 of 44 (16%) breast cancer biopsies. A restriction fragment length polymorphism assay was designed to distinguish between HMLVs and MMTVs, and upon analyses, PCR amplicons appeared to be HMLVs. To confirm these findings, amplicons from the T47D cell line and from four randomly selected breast cancer patients were sequenced. Of 106 DNA sequences obtained, 103 were homologous with a short arm of human chromosome (Chr) 3 (3p13), two with Chr 4, and one with Chr 8. None of the sequences exhibited significant nucleotide homology with MMTVs, HMLVs, or with HERVs (all <50%). Thus, we conclude that (i) HMLVs are integral members of the MMTV family; (ii) MMTVs/HMLVs are genetically distinct from HERVs; (iii) MMTV/HMLV DNA is not present in human breast cancer cell lines or clinical biopsies in our locality.

Adult↗
PubMed2004

Pathogenesis of breast carcinoma.

Breast cancer usually develops after a series of epithelial changes in the terminal ductolobular unit. There are multiple benign causes of breast lumps, the majority of which are not associated with an increased risk of breast cancer. Histological changes of pre-malignancy such as atypical hyperplasia and in situ carcinoma can be identified, and these are indications for either close surveillance or further surgery. At the time of diagnosis, breast cancers can be staged both clinically and pathologically, and this facilitates international comparisons of results of treatment.

Breast Diseases↗
PubMed2004

Pathology of breast carcinoma.

The pathologist examines biopsy material obtained at surgery or preoperatively by core biopsy to make a definitive diagnosis of malignancy and to determine the type and grade of the tumour. Additional prognostic information is provided to the clinician, and this includes the true tumour size and the relative contribution of the in situ and invasive components. Other important factors include multifocality, vascular invasion and the presence and extent of axillary nodal metastases. For optimal use of this important information, close cooperation between the members of the multidisciplinary team is essential.

Adult↗
PubMed2004

A viral aetiology for breast cancer: time to re-examine the postulate.

Despite decades of research, no aetiologic factor(s) for human breast cancer has been identified and the search for a causal agent has all but been abandoned during the past thirty years. Over 60 years ago, it was demonstrated that breast tumours in mice are caused by an oncornavirus, murine mammary tumour virus (MMTV). Whilst many at that time postulated a similar virus might be the causative agent of human breast cancer, genetic evidence was difficult to obtain primarily because of the occurrence of endogenous human retrovirus (HER) sequences within the human genome that share extensive regions of nucleotide homology with MMTV. Recently, there has been a resurgence of interest in the possibility that a significant proportion of human breast cancers may be caused by viral infections. Two candidate viruses have been proposed, a human retroviral analogue of MMTV (which differs significantly in sequence and characteristics from HERs) and, the Epstein-Barr virus (gamma-herpes virus). These two viruses have been reported to occur in up to 37 and 50% of breast cancer cases, respectively. Here we present the background to the infectious hypothesis for the aetiology of breast cancer and review recent findings.

Breast Neoplasms↗
PubMed2003

Combination of microdissection and microarray analysis to identify gene expression changes between differentially located tumour cells in breast cancer.

Comparison of gene expression changes between cancer cells at the periphery and in the centre of breast cancers was performed using a combination of microdissection and microarray analysis. Cancer cells from the two areas were pooled separately from five patients with ductal carcinoma in situ and separately from five patients with frankly invasive cancer. Limited total RNA, 100-200 ng, from this microdissected tissue required use of the Atlas SMART trade mark Probe Amplification Kit to synthesize and amplify cDNA and make (33)P-labelled probes. Probes were then hybridized to Atlas Human Cancer 1.2 Arrays containing 1176 known genes. Triplicate analysis revealed that 22 genes changed their expression levels in the periphery relative to the central region: 15 upregulated and seven downregulated (arbitrary threshold of 1.5-fold or greater). Differences in RNA levels were confirmed by quantitative real-time PCR for two of the genes and by changes in protein levels, detected by immunohistochemistry, for a couple of representative gene products. Thus, changes in gene expression associated with variation in microanatomical location of neoplastic cells can be detected within even small developing tumour masses.

Adenocarcinoma↗
PubMed2002

Paget disease of the nipple: a multifocal manifestation of higher-risk disease.

BACKGROUND: The treatment of Paget disease by mastectomy has been challenged recently in favor of breast-conserving techniques. A large series of patients treated with mastectomy has been reviewed to assess the feasibility of less radical surgery. METHODS: The cases of 70 women with a clinical diagnosis of Paget disease were reviewed. The type, grade, receptor and node status, and the mammographic and pathologic extent of the underlying breast malignancy were determined. The survival of patients with invasive disease was compared with matched controls without Paget disease. RESULTS: The underlying malignancy was invasive in 58% of cases. Despite the fact that only one third of women presented with a palpable mass, the malignancy was frequently extensive, being confined to the retroareolar region in only 25% of cases. The true extent of the disease was underestimated by mammography in 43% of cases. Of the patients with ductal in situ carcinoma, 96.5% had high-grade carcinomas and 100% had invasive carcinomas of high cytonuclear grade. Overexpression of the c-erb-B2 oncogene was detectable in 83% of cases. Patients with Paget disease had a significantly worse survival than matched controls, but this difference was eliminated if they were also matched for c-erb-B2 status. CONCLUSIONS: Paget disease is often associated with extensive underlying malignancy, which is difficult to assess accurately either clinically or mammographically. As a consequence, cone excision of the nipple would have resulted in incomplete excision in 75% of cases. The underlying disease is of high grade and is frequently c-erb-B2 positive with a resulting poor prognosis. Aggressive local and systemic treatment would seem to be merited.

Adult↗
PubMed2002

Breast carcinoma in women age 25 years or less.

BACKGROUND: Although several studies have examined breast carcinoma in young women aged < or = 35 years at diagnosis, there are only occasional cases reported in very young women aged < or = 25 years, and, to the authors' knowledge, no series are available. The presentation, tumor biology, behavior, and outcome of breast carcinoma in very young women are not known, and the rarity of breast malignancy within this age group could lead to diagnostic delays. METHODS: The tumor characteristics and survival of 15 women aged < or = 25 years at the time of diagnosis, have been reviewed and compared with women aged 26-35 years under the care of Guy's Hospital's Breast Unit during the same period of time. Where appropriate, the two groups were individually matched for tumor size (clinical measurement) and histologic grade. RESULTS: Fifteen cases were examined, with a median follow-up of 108 months and a median age of 24 years. The median duration of symptoms was 4 weeks, and the median tumor size was 20 mm. Two patients had ductal carcinoma in situ (DCIS) only, while the other 13 patients had invasive carcinomas, none of which were Grade I. A mastectomy was performed on 8 out of 15 patients (53%). Axillary nodal metastases were present in 4 out of 12 patients (33%). Of the 13 cases of invasive disease, 9 out of 13 patients (69%) experienced recurrence and died of breast carcinoma. Median disease free survival for patients with invasive disease was 86 months. There was no difference in overall survival between the patients aged < or = 25 years and those aged 26-35, but taken together young women < or = 35 had a worse prognosis than women between 36 and 65, due to a higher incidence of high grade and estrogen receptor negative tumors. CONCLUSIONS: The current study suggests that among young women with breast carcinoma there is no difference in prognosis between the very young and the young. Despite two thirds of patients being node negative, the high mortality rate indicates a need for an optimal selection of adjuvant therapy among these cases.

Adolescent↗