Leptin-regulated gene expression in MCF-7 breast cancer cells: mechanistic insights into leptin-regulated mammary tumor growth and progression

Perera, Candida N.; Chin, Hwei G; Duru, Nadire; Camarillo, Ignacio G.

doi:10.1677/joe-08-0215e

Cited by 13 publications

(16 citation statements)

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“…Because of the increasing number of obese breast cancer patients, the mechanism of this phenomenon is currently under investigation. Multiple evidence in cellular and animal breast cancer models indicate that leptin, the major hormone produced by fat tissue, can also be involved in the pathogenesis and maintenance of breast cancer (Carroll 2003, Perera et al 2008.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, obesity has assumed epidemic proportions in industrialized Western countries, and has been linked to increased risk for a series of cancers, in particular those characterized by hormone dependence such as postmenopausal breast and ovarian cancers (Rodriguez et al 2001, Carroll 2003, Stephenson & Rose 2003, Moore et al 2008, Perera et al 2008. Increased fat mass and body mass index are the typical features of human obesity and are associated with an increased secretion of the adipocyte-derived hormone, leptin.…”

Section: Introductionmentioning

confidence: 99%

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Cellular and molecular crosstalk between leptin receptor and estrogen receptor-α in breast cancer: molecular basis for a novel therapeutic setting

Fusco¹,

Galgani²,

Procaccini³

et al. 2010

Endocrine-Related Cancer

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Obesity is associated with an increased risk of breast cancer. A number of adipocytokines are increased in obesity causing low-level chronic inflammation associated with an increased risk of tumors. The adipocytokine leptin shows profound anti-obesity and pro-inflammatory activities. We have hypothesized that in common obesity, high circulating leptin levels might contribute to an increased risk of breast cancer by affecting mammary cell proliferation and survival. Leptin exerts its activity not only through leptin receptor (LepR), but also through crosstalk with other signaling systems implicated in tumorigenesis. In this study, we focused our attention on the relationship between the leptin/LepR axis and the estrogen receptor-a (ERa). To this aim, we utilized two human breast cancer cell lines, one ERa-positive cell line (MCF 7) and the other ERa-negative cell line (MDA-MB 231). We observed that the two cell lines had a different sensitivity to recombinant leptin (rleptin): on MCF 7 cells, rleptin induced a strong phosphorylation of the signal transducer and activator of transcription (STAT) 3 and of the extracellular related kinase 1/2 pathways with an increased cell viability and proliferation associated with an increased expression of ERa receptor. This response was not present in the MDA-MB 231 cells. The effects induced by leptin were lost when LepR was neutralized using either a monoclonal inhibitory antibody to LepR or LepR genesilencing siRNA. These data suggest that there is a bidirectional communication between LepR and ERa, and that neutralization and/or inactivation of LepR inhibits proliferation and viability of human breast cancer cell lines. This evidence was confirmed by ex vivo studies, in which we analyzed 33 patients with breast cancer at different stages of disease, and observed that there was a statistically significant correlation between the expression of LepR and ERa. In conclusion, this study suggests a crosstalk between LepR and ERa, and could envisage novel therapeutic settings aimed at targeting the LepR in breast cancers.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cellular and molecular crosstalk between leptin receptor and estrogen receptor-α in breast cancer: molecular basis for a novel therapeutic setting

Fusco¹,

Galgani²,

Procaccini³

et al. 2010

Endocrine-Related Cancer

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“…In addition, Villin 2 participates in controlling the growth of cancer cells and, as an important metastasis-associated molecule, it is over-expressed in various tumors (26)(27)(28)(29)(30). Microarray array analysis has revealed increased levels of Villin 2 expressed in conjunction with up-regulation of the gene for leptin, which plays a role in mammary tumor growth (31). Also, in colon cancer cells (CRCs), Villin 2 forms a complex between L1CAM and lKB, and participates in L1CAM-mediated metastasis with nuclear factor-kB signaling (32).…”

Section: Functional Analysis Of Villin 2 Proteinmentioning

confidence: 99%

Functional study of Villin 2 protein expressed in longissimus dorsi muscle of Korean native cattle in different growth stages

Jin

Han²,

Xu³

et al. 2012

BMB Reports

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The aim of this study was to investigate protein profiles related to the induction of adipogenesis within the bovine longissimus dorsi muscle (BLDM) by proteomic analysis. We analyzed BLDM proteins at different growth stages to clarify the physiological mechanisms of marbled muscle development in 20 head of Korean native cattle (11 month: 10 head, 17 month: 10 head). BLDM proteins were analyzed by two-dimensional electrophoresis and image analysis. Villin 2 was specifically identified by mass spectrometry and a protein search engine. Villin 2 protein expression in BLDM decreased during the fat development stage in test steers. In a Western blot cell culture study of spontaneously immortal bovine muscle fibroblasts, the abundance of Villin 2 was shown to be down-regulated during differentiation into muscle. In 3T3-L1 mouse embryonic fibroblasts, Villin 2 was decreased during differentiation into adipocytes. The results suggest that Villin 2 may be related to the induction of transdifferentiation and adipogenesis in bovine longissimus dorsi muscle. [BMB reports 2012; 45(2): 102-107]

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“…In vitro studies have shown that leptin stimulates proliferation of normal and cancerous mammary epithelial cells [7,19]. Furthermore, leptin has been shown to promote tumor growth by other mechanisms including inhibition of apoptosis, enhancement of cell invasion and expression of matrix degrading enzymes [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Chronic Leptin Treatment Sensitizes MCF-7 Breast Cancer Cells to Estrogen

Valle

Sastre‐Serra

Oliver

et al. 2011

Cell Physiol Biochem

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Background/Aims: Obesity is associated with an increased risk of estrogen-dependent breast cancer. The adipokine leptin, whose levels are chronically increased in obese people, has been shown to stimulate ER positive cancer cell growth. Considering previous evidence of a crosstalk between leptin and estrogen signaling, the objective of this study was to establish the influence of chronic leptin treatment on estrogen-dependent cell growth. Methods: To this aim, we use the estrogen receptor (ER) positive MCF-7 breast cancer cell line treated chronically with leptin and analyzed estrogen-dependent cell growth, ERs (ERα and ERβ) expression, ER-dependent transcriptional activity as well as cell survival to the antiestrogenic agents tamoxifen and ICI 182,780. Results: Leptin signaling pathway kept activated after chronic stimulation (7 days) with leptin showing significant phosphorylation of JAK2 and STAT3 and higher cell proliferation rate. Chronic leptin at 100 ng/mL dose increased ERα to ERβ ratio and consistently enhanced estrogen-dependent transcriptional activity, increasing E2-dependent cell growth and resistance to antiestrogen agents. Conclusion: This study supports the existence of a crosstalk between leptin and estrogen, in which leptin might play an important role potentiating the mitogenic action of estrogen, probably by alteration of ERα to ERβ ratio.

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Leptin-regulated gene expression in MCF-7 breast cancer cells: mechanistic insights into leptin-regulated mammary tumor growth and progression

Cited by 13 publications

References 0 publications

Cellular and molecular crosstalk between leptin receptor and estrogen receptor-α in breast cancer: molecular basis for a novel therapeutic setting

Cellular and molecular crosstalk between leptin receptor and estrogen receptor-α in breast cancer: molecular basis for a novel therapeutic setting

Functional study of Villin 2 protein expressed in longissimus dorsi muscle of Korean native cattle in different growth stages

Chronic Leptin Treatment Sensitizes MCF-7 Breast Cancer Cells to Estrogen

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