The expression of FHIT, PCNA and EGFR in benign and malignant breast lesions

Terry, George; Ho, Linda; Londesborough, P.; Duggan, Catherine; Hanby, Andrew M.; Cuzick, Jack

doi:10.1038/sj.bjc.6603512

Cited by 16 publications

(15 citation statements)

References 36 publications

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“…The WA-mediated reduction in cellular proliferation in vivo in the tumor was confirmed by immunohistochemical analysis for PCNA expression. The PCNA is a marker for cellular proliferation and is expressed in >90% of in situ and invasive breast carcinomas (39). The PCNA expression was about 50% lower in tumors from WA-treated mice compared with control tumors (Fig.…”

Section: Resultsmentioning

confidence: 99%

Withaferin A Causes FOXO3a- and Bim-Dependent Apoptosis and Inhibits Growth of Human Breast Cancer Cells In vivo

et al. 2008

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Withaferin A (WA) is derived from the medicinal plant Withania somnifera, which has been safely used for centuries in Indian Ayurvedic medicine for treatment of different ailments. We now show, for the first time, that WA exhibits significant activity against human breast cancer cells in culture and in vivo. The WA treatment decreased viability of MCF-7 (estrogen-responsive) and MDA-MB-231 (estrogenindependent) human breast cancer cells in a concentrationdependent manner. The WA-mediated suppression of breast cancer cell viability correlated with apoptosis induction characterized by DNA condensation, cytoplasmic histone-associated DNA fragmentation, and cleavage of poly-(ADP-ribose)-polymerase. On the other hand, a spontaneously immortalized normal mammary epithelial cell line (MCF-10A) was relatively more resistant to WA-induced apoptosis compared with breast cancer cells. The WAmediated apoptosis was accompanied by induction of Bim-s and Bim-L in MCF-7 cells and induction of Bim-s and Bim-EL isoforms in MDA-MB-231 cells. The cytoplasmic histone-associated DNA fragmentation resulting from WA exposure was significantly attenuated by knockdown of protein levels of Bim and its transcriptional regulator FOXO3a in both cell lines. Moreover, FOXO3a knockdown conferred marked protection against WA-mediated induction of Bim-s expression. The growth of MDA-MB-231 cells implanted in female nude mice was significantly retarded by 5 weekly i.p. injections of 4 mg WA/kg body weight. The tumors from WA-treated mice exhibited reduced cell proliferation and increased apoptosis compared with tumors from control mice. These results point toward an important role of FOXO3a and Bim in regulation of WA-mediated apoptosis in human breast cancer cells. [Cancer Res 2008;68(18):7661-9]

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Section: Resultsmentioning

confidence: 99%

Withaferin A Causes FOXO3a- and Bim-Dependent Apoptosis and Inhibits Growth of Human Breast Cancer Cells In vivo

et al. 2008

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“…In this study, we found 3p24.3 LOH in 31% of IDC and only in 6.7% of ILC, which may suggest an involvement of THRB in the development of ductal breast carcinomas. In sporadic breast cancer, LOH within the FHIT gene has been observed at frequencies that vary from 25% to 45% [10,11], and FHIT underexpression is found in 41% of invasive breast carcinomas [23]. Deletions of this gene have also been observed in preneoplastic lesions [24] and in normal and benign regions surrounding the tumor in patients with BRCA1/2 mutations [9], suggesting that FHIT deletions could be an early event in breast tumorigenesis.…”

Section: Discussionmentioning

confidence: 98%

Differential loss of heterozygosity profile on chromosome 3p in ductal and lobular breast carcinomas

Oliveira

Lima

et al. 2012

Human Pathology

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“…Loss of Fhit and Wwox has been shown to be an important step in the initiation of tumorigenesis in a variety of solid tumors including lung, breast, colorectal, and gastric cancers to name a few 19–22. In lung cancer sections, Fhit loss has been reported to occur in dysplasia and prior to alterations in p53 23.…”

Section: Discussionmentioning

confidence: 99%

Coordinate Loss of Fragile Gene Expression in Pancreatobiliary Cancers: Correlations Among Markers and Clinical Features

et al. 2009

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Background Loss of expression of fragile gene products, Fhit and Wwox, occurs in many cancer types, with loss exhibited early in the neoplastic process in some. Wwox has been understudied in pancreatobiliary cancers, especially in relation to other involved tumor suppressors. We have assessed the status of the Fhit and Wwox proteins encoded by DNA damage susceptible chromosome fragile sites encompassed by FHIT and WWOX tumor suppressor genes. Methods Pancreatic, gallbladder and ampullary cancers, normal pancreas, chronic pancreatitis, and benign gall-bladder specimens were stained for expression of Fhit, Fhit effector protein Fdxr, Wwox, and other tumor suppressors by immunohistochemistry, and comparisons were made between benign and malignant tissue. Correlations of expression among proteins and clinicopathologic features were sought using Spearman’s rank order. Survival curves were created using the Kaplan-Meier method and compared by log-rank analysis. Predictors of survival were determined using multivariate Cox proportional hazards analysis. Results Fhit and Wwox were ubiquitously expressed in benign samples and significantly and coordinately reduced in pancreatic, gallbladder, and ampullary cancers. In pancreatic cancers, Fdxr expression was positively correlated with Fhit and Wwox expression. Neither Fhit nor Wwox expression correlated with expression of other tumor suppressors or with clinicopathologic characteristics measured. Conclusion Loss of Fhit and Wwox expression does not predict tumor progression or patient survival, suggesting that loss of expression of genes at the exquisitely replication stress sensitive chromosome fragile regions is an early event in the pathogenesis of cancers of the gallbladder, pancreas, and ampulla.

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The expression of FHIT, PCNA and EGFR in benign and malignant breast lesions

Cited by 16 publications

References 36 publications

Withaferin A Causes FOXO3a- and Bim-Dependent Apoptosis and Inhibits Growth of Human Breast Cancer Cells In vivo

Withaferin A Causes FOXO3a- and Bim-Dependent Apoptosis and Inhibits Growth of Human Breast Cancer Cells In vivo

Differential loss of heterozygosity profile on chromosome 3p in ductal and lobular breast carcinomas

Coordinate Loss of Fragile Gene Expression in Pancreatobiliary Cancers: Correlations Among Markers and Clinical Features

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