Leptin and cancer

Garofalo, Cecilia; Surmacz, Eva

doi:10.1002/jcp.20472

Cited by 556 publications

(518 citation statements)

References 209 publications

Supporting

Mentioning

500

Contrasting

Unclassified

Order By: Relevance

“…[18][19][20][21] Studies in cellular and animal models strongly suggested that high levels of leptin might promote breast carcinogenesis. 3 Reports from our and other laboratories demonstrated that both leptin and ObR are overexpressed in breast cancer cells, 4,6,33 which implies that leptin could promote breast cancer not only through endocrine but also through autocrine mechanisms. As reported by us before, leptin synthesis in breast cancer cells can be upregulated by obesity-related stimuli, such as high levels of insulin, insulin-like growth factor I, or estrogens.…”

Section: Discussionmentioning

confidence: 97%

“…2 Recent studies in cellular and animal models provided strong evidence that leptin can be involved in neoplastic processes, for instance, in the development and progression of breast, colorectal, and endometrial cancers. [3][4][5] In addition, both leptin and its receptor (ObR) have been detected in different neoplastic tissues, usually at levels higher than that in respective normal tissues. [6][7][8] Interestingly, overexpression of the leptin system in breast cancer appears to be associated with higher tumor grade and size.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Functional analysis of the ‐2548G/A leptin gene polymorphism in breast cancer cells

Terrasi

Fiorio

Mercanti

et al. 2009

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Leptin is overexpressed in human breast tumors and is produced by breast cancer cells in response to obesity‐related stimuli. The leptin promoter polymorphism Lep‐2548G/A can be associated with increased leptin secretion by adipocytes and elevated cancer risk. However, molecular mechanisms underlying the link between Lep‐2548G/A and breast cancer have never been addressed. Lep‐2548G/A is proximal to a binding site for the transcriptional factor Sp1. Furthermore nucleolin, a transcriptional repressor, can bind Sp1 or its consensus site. Consequently, we focused on the impact of Lep‐2548G/A on Sp1‐ and nucleolin‐dependent leptin transcription in breast cancer cells. The Lep‐2548G/A was identified in a homozygous conformation in BT‐474 and SK‐BR‐3 breast cancer cells, in a heterozygous conformation in MDA‐MB‐231 cells, and a wild‐type Lep‐2548G/G sequence was present in MCF‐7 and ZR‐75‐1 cells. The occurrence of Lep‐2548A/A and Lep‐2548G/A coincided with high and intermediate leptin mRNA expression, respectively, while cells containing Lep‐2548G/G expressed low leptin mRNA levels. We demonstrated that the existence of Lep‐2548G/A improved efficient recruitment of Sp1 to DNA under insulin treatment, while Sp1 loading on DNA containing Lep‐2548G/G was not insulin‐dependent. In contrast, nucleolin binding to Lep‐2548G/A was downregulated in response to insulin, while it was not regulated on Lep‐2548G/G. The presence of Lep‐2548G/A was studied in breast cancer epithelial cells by IHC and LCM. Interestingly, all 14 tumors expressing high leptin levels contained Lep‐2548A/A. In conclusion, the occurrence of Lep‐2548G/A can enhance leptin expression in breast cancer cells via Sp1‐ and nucleolin‐dependent mechanisms and possibly contribute to intratumoral leptin overexpression. © 2009 UICC

show abstract

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Functional analysis of the ‐2548G/A leptin gene polymorphism in breast cancer cells

Terrasi

Fiorio

Mercanti

et al. 2009

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has been demonstrated that obesity increases the risk of breast cancer in postmenopausal females by 30-50%, a high body mass index has been identified to correlate markedly with an increased risk of inflammatory breast cancer in premenopausal and postmenopausal populations (8). However, the molecular mechanisms of obesity-induced breast carcinogenesis remain unclear.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, studies have observed that leptin is capable of modulating several other processes, including angiogenesis (15), fertility (16) and immune response (17). In addition, evidence suggests that leptin may be involved in tumorigenesis, particularly in the development of breast, colorectal and prostate cancer (8). Breast cancer patients exhibited significantly higher leptin levels compared with the corresponding controls (18) and the expression of leptin and leptin receptors is more frequent in larger tumors (19).…”

Section: Introductionmentioning

confidence: 99%

Leptin promotes the proliferation and migration of human breast cancer through the extracellular-signal regulated kinase pathway

Sun

2013

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Obesity has been associated with an increased risk of postmenopausal breast cancer, which may be due to the expression of leptin. The aim of this study was to determine the role of leptin in the growth of breast cancer cells in nude mice, the proliferation and migration of MCF-7 human breast cancer cells and its downstream signaling pathway. The xenograft mouse model was elicited by injecting MCF-7 human breast cancer cells into the left back axilla and the tumor size was measured every other day. Leptin injected subcutaneously around the tumor site led to an increase in the size and weight of the tumor, whereas the leptin antagonist (LA) significantly inhibited the size and weight of the tumor. Leptin promoted the proliferation and migration of MCF-7 cells and LA inhibited it. The effects of leptin on increasing the size and weight of the tumor in the nude mice and the proliferation and migration of MCF-7 human breast cancer cells were eradicated by pretreatment with LA, the extracellular-signal regulated kinase (ERK) inhibitor PD98059. In the xenograft mouse model the leptin level was increased and leptin increased the phosphorylation of ERK in the MCF-7 cells, whereas LA significantly reduced the phosphorylation of ERK. These results indicated that leptin promotes the growth of breast cancer in the nude mice and increases the proliferation and migration of MCF-7 human breast cancer cells via the ERK pathway.

show abstract

“…2000). LEP activates several intracellular pathways implicated in breast carcinogenesis, including the phosphoinositide‐3/Akt kinase signaling pathway (Garofalo and Surmacz 2006; Jarde et al. 2009).…”

Section: Introductionmentioning

confidence: 99%

Voluntary physical activity counteracts the proliferative tumor growth microenvironment created by adipose tissue via high-fat diet feeding in female rats

Theriau

Connor

2017

Physiol Rep

View full text Add to dashboard Cite

The adipokine secretion profile created from adipose tissue may represent the molecular mechanism behind the obesity‐breast cancer association. Two adipokines, adiponectin (ADIPO), and leptin (LEP), are altered with obesity and exert antagonistic effects on breast cancer proliferation. We set out to determine whether the adipose‐dependent tumor promoting growth environment created by a high‐fat diet (HFD) in female Sprague‐Dawley rats is altered compared to established responses in male rats and whether voluntary physical activity (PA) ameliorates any HFD‐dependent effects. We found that conditioned media (CM) created from the adipose tissue of female HFD‐fed rats increased the proliferation of MCF7 cells compared to those cells grown in CM prepared from lean adipose tissue. HFD‐CM inhibited AMPK and activated Akt signaling, decreased p27 phosphorylation at T198, reduced total p27 and AdiporR1 protein levels and promoted cell‐cycle entry. PA reversed the proliferative effects of HFD‐CM on MCF7 cells by preventing the effects of HFD on AMPK, Akt, p27 and AdipoR1, ultimately resulting in cell‐cycle withdrawal. Overexpressing AdipoR1 abolished the proliferative effects of the HFD‐CM on MCF7 cells and enhanced the anti‐proliferative effects PA on the HFD‐CM. Thus, PA represents a means to prevent deleterious obesity‐related alterations in tumor growth environment which are brought about by changes in adipokine secretion profile from adipose tissue in the presence of estrogen. Furthermore, although adipose produces hundreds of adipokines, the ADIPO:LEP ratio may serve to indicate the contribution of adipose in creating a tumor growth microenvironment.

show abstract

Leptin and cancer

Cited by 556 publications

References 209 publications

Functional analysis of the ‐2548G/A leptin gene polymorphism in breast cancer cells

Functional analysis of the ‐2548G/A leptin gene polymorphism in breast cancer cells

Leptin promotes the proliferation and migration of human breast cancer through the extracellular-signal regulated kinase pathway

Voluntary physical activity counteracts the proliferative tumor growth microenvironment created by adipose tissue via high-fat diet feeding in female rats

Contact Info

Product

Resources

About