Oestrogen-regulated genes in breast cancer: Association of pLIV1 with lymph node involvement

Manning, David L.; Robertson, J. F. R.; Ellis, Ian O.; Elston, C. W.; McClelland, Richard Andrew; Gee, Julia Margaret Wendy; Jones, R. J.; Green, C. D.; Cannon, P.; Blamey, R.W.; Nicholson, Robert Ian

doi:10.1016/0959-8049(94)90543-6

Cited by 90 publications

(84 citation statements)

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“…Indeed, given the complex mechanisms resulting in controlled cellular growth and development and the heterogeneous nature of tumour cell populations, it seems unlikely that any single marker analysis will ever prove infallible in detecting the endocrine-sensitive phenotype. While this is as undoubtedly true for pLIV 1 as for any other oestrogen-regulated gene, its additional potential as a marker of lymph node involvement (Manning et al, 1994) holds promise and is under investigation in our laboratories.…”

Section: Discussionmentioning

confidence: 99%

Oestrogen-regulated genes in breast cancer: association of pLIV1 with response to endocrine therapy

McClelland

Manning²,

Gee³

et al. 1998

Br J Cancer

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Summary Northern hybridization analyses of the oestrogen-inducible mRNAs pLIV1 and pS2 were compared with oestrogen receptor (ER) immunocytochemistry assessments in 40 untreated primary or early recurrent breast tumours. Significant associations were observed between pLIVl/ER (P < 0.03), pS2/ER (P < 0.001) and pLIV1/pS2 (P < 0.04) status. After disease recurrence, patients were treated with assessable courses of endocrine therapies. Positive pLIV1, pS2 and ER statuses in primary disease were consequently found to be predictive of endocrine responsiveness in the secondary lesions (P < 0.03, P < 0.02, P < 0.005 respectively). However, despite these associations, a number of pLIV1i-and/or pS2-positive tumours failed to respond to therapy.Keywords: oestrogen-regulated genes; breast cancer; oestrogen receptor The selection of breast cancer patients for endocrine therapy is most frequently made on the basis of tumour oestrogen-receptor (ER) protein content. However, the predictive capability of ER status alone is not absolute (Nicholson et al, 1991). While few ERnegative patients respond to such therapies, perhaps half of ERpositive patients will also gain no clinically defined benefit. It has been postulated that coassessment of ER and oestrogeninducible genes or protein products, as markers of functioning ER-mediated cellular growth mechanisms, might give better predictive results. As such, the additional measurements of tumour PR and pS2 protein content have been shown to partly improve selectivity (Horwitz and McGuire, 1977;Foekens et al, 1990).Our study evaluates the significance of expression of the oestrogen-inducible pLIVl (Manning et al, 1988) 13 as grade 2 and 22 as grade 3. Twenty-seven tumours were described as infiltrating ductal (no special type), five mixed/tubular, two mixed ductal/lobular and the remainder as single cases of lobular, medullary, atypical medullary, mixed ductal/mucinous and ductal carcinoma in situ.

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Section: Discussionmentioning

confidence: 99%

Oestrogen-regulated genes in breast cancer: association of pLIV1 with response to endocrine therapy

McClelland

Manning²,

Gee³

et al. 1998

Br J Cancer

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“…Low levels of zinc have been observed in several malignancies, such as those of the liver, gallbladder, digestive tract, and prostate (54)(55)(56). Conversely, both high and low levels of zinc have been found in breast cancers (54,(57)(58).…”

Section: Zincmentioning

confidence: 99%

“…ZIP4 has been reported to increase cell proliferation through zinc transport, resulting in tumor growth, most specifically in pancreatic cancer (44,55). Both ZIP6 and ZIP10 have roles in the progression and metastasis of breast cancer (46,(57)(58) and ZIP1 has been suggested as a tumor suppressor of prostate cancer (56). Thus, by disrupting the distribution of zinc in tissues, altered levels of zinc transporters may enhance the development of various tumors, indicating the potential of zinc as an anticancer agent.…”

Section: Zincmentioning

confidence: 99%

“…Low levels of zinc have been observed in several malignancies, such as those of the liver, gallbladder, digestive tract, and prostate (54-56). Conversely, both high and low levels of zinc have been found in breast cancers (54,(57)(58).Consequently, it is no surprise that an association between zinc transporter levels and cancer progression has also been proposed (51, 59). Multiple zinc transporters, including ZIP4, ZIP6, ZIP10, and ZIP1, have been identified as factors in the progression of various types of cancer.…”

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confidence: 99%

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New applications of old metal-binding drugs in the treatment of human cancer

Dou¹

2012

Front Biosci

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Significant advances in the use of metal complexes, precipitated by platinum, have fostered a renewed interest in harnessing their rich potential in the treatment of cancer. In addition to platinum-based complexes, the anticancer properties of other metals such as ruthenium have been realized, and ruthenium-based compounds are currently being investigated in clinical trials. Since the process of drug development can be expensive and cumbersome, finding new applications of existing drugs may provide effective means to expedite the regulatory process in bringing new drugs to the clinical setting. Encouraging findings from laboratory studies reveal significant anticancer activity from different classes of metal-chelating compounds, such as disulfiram, clioquinol, and dithiocarbamate derivatives that are currently approved for the treatment of various pathological disorders. Their use as coordination complexes with metals such as copper, zinc, and gold that target the ubiquitin-proteasome pathway have shown significant promise as potential anticancer agents. This review discusses the unique role of several selected metals in relation to their anti-cancer properties as well as the new therapeutic potential of several previously approved metal-chelating drugs. In vitro and in vivo experimental evidence along with mechanisms of action (e.g., via targeting the tumor proteasome) will also be discussed with anticipation of strengthening this exciting new concept. KeywordsDisulfiram; Clioquinol; Dithiocarbamates; Copper; Zinc; Ubiquitin-Proteasome Pathway; Proteasome Inhibitor; Chymotrypsin-Like Activity; Review INTRODUCTION The use of metal complexes for cancer treatmentThe development of metal-based complexes for the treatment of cancer began with the discovery of the anti-cancer properties of cisplatin in the early 1960s (Figure 1). Over 90% of testicular cancer cases have been cured by cisplatin, and it has also been important in the treatment of several other types of cancer, including ovarian, cervical, bladder, head and neck, melanoma, and lymphomas (1). Cisplatin interacts with DNA and forms adducts which interfere with the replication and transcription processes, and ultimately triggers apoptosis (2). These cisplatin-DNA interactions have been extensively studied, and it has been clearly shown that a (Pt)-GG intrastrand cross-link is responsible for the cytotoxicity of Send correspondence to: Qing Ping Dou, The Developmental Therapeutics Program, Barbara Ann Karmanos Cancer Institute, and Departments of Oncology, Pharmacology and Pathology, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA, doup@karmanos.org. NIH Public Access Author ManuscriptFront Biosci (Schol Ed). Author manuscript; available in PMC 2013 May 07. Published in final edited form as:Front Biosci (Schol Ed). ; 4: 375-391. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript cisplatin (3). However, the toxicities associated with cisplatin, coupled with intrinsic and acquired drug resistance, ha...

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“…Zinc plays various roles in cell metabolism and is involved in cellular processes such as cell growth, differentiation and gene transcription (2,3), suggesting that its altered distribution might promote tumorigenesis. LIV-1 was originally identified as an estrogen-induced gene in the breast cancer cell line ZR-75-1 (4) and its expression was also shown to be correlated with lymph node involvement of the breast carcinoma, indicating a role for LIV-1 in metastasis (5).…”

Section: Introductionmentioning

confidence: 99%

LIV-1 enhances the aggressive phenotype through the induction of epithelial to mesenchymal transition in human pancreatic carcinoma cells

Unno

Satoh

Hirota³

et al. 2009

Int J Oncol

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Abstract. LIV-1 is a downstream target of STAT3 and is essential for the nuclear localization of Snail, a master regulator of epithelial to mesenchymal transition (EMT). Little is known about the association of LIV-1 with pancreatic carcinoma development, therefore, expression of LIV-1 mRNA was analyzed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in 9 cultured cell lines (8 carcinoma and 1 normal duct cell lines) and 24 pancreatic tissues (12 carcinoma and 12 normal tissues). Localization of this gene product was investigated by immunohistochemistry in 72 pancreatic carcinoma and the relation between its expression and clinicopathological findings was examined. To assess the function of LIV-1 in pancreatic carcinoma cells, stable siRNA expressing Panc-1 cells were generated. Higher expression of LIV-1 mRNA was found in both pancreatic carcinoma cell lines and pancreatic carcinoma tissues compared to normal duct cell line and histologically normal tissues, respectively. Immunohistochemical analysis revealed that LIV-1 expression was frequently found in 76.4% of pancreatic carcinoma tissues and its expression level was associated with tumor size and lymphatic infiltration. Down-regulated LIV-1 cells showed significant inhibition of anchorage-dependent or -independent proliferation and cell motility in vitro and reduction of tumor growth and metastasis in vivo. Furthermore, nuclear expression of Snail was decreased and E-cadherin expression was restored in LIV-1 siRNA expressing pancreatic carcinoma cells. These findings indicate that LIV-1 may be involved in acquisition of the aggressive phenotype of human pancreatic carcinoma cells through the induction of epithelial to mesenchymal transition. IntroductionLIV-1 is a member of new subfamily of zinc transporters, termed LZT (LIV-1 subfamily of ZIP zinc transporters) and is suggested to be located to the plasma membrane. It has been shown to act as a zinc transporter, leading to an increase in intracellular zinc levels (1). Zinc plays various roles in cell metabolism and is involved in cellular processes such as cell growth, differentiation and gene transcription (2,3), suggesting that its altered distribution might promote tumorigenesis. LIV-1 was originally identified as an estrogen-induced gene in the breast cancer cell line ZR-75-1 (4) and its expression was also shown to be correlated with lymph node involvement of the breast carcinoma, indicating a role for LIV-1 in metastasis (5).Epithelial to mesenchymal transition (EMT) is a general phenomenon that is an essential event in embryonic development, tissue remodelling and wound repair. During EMT, a loss of intracellular adhesion is observed along with extensive remodelling of the cytoskeleton and expression of components specific to a mesenchymal phenotype. Epithelial cells undergoing the transition to a mesenchymal phenotype also display an increased propensity for migration (6-8). Therefore, this transition is considered to be an important event during malignant tumor progression an...

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Oestrogen-regulated genes in breast cancer: Association of pLIV1 with lymph node involvement

Cited by 90 publications

References 10 publications

Oestrogen-regulated genes in breast cancer: association of pLIV1 with response to endocrine therapy

Oestrogen-regulated genes in breast cancer: association of pLIV1 with response to endocrine therapy

New applications of old metal-binding drugs in the treatment of human cancer

LIV-1 enhances the aggressive phenotype through the induction of epithelial to mesenchymal transition in human pancreatic carcinoma cells

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