Identification of leptin receptors in human breast cancer: functional activity in the T47-D breast cancer cell line

Laud, Karine; Gourdou, Isabelle; Pessemesse, Laurence; Jp, Peyrat; Djiane, Jean

doi:10.1016/s0303-7207(01)00678-5

Cited by 177 publications

(178 citation statements)

References 33 publications

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“…Leptin receptors are expressed in human breast tumors and breast cancer cell lines and the addition of leptin increases cell proliferation. [46][47][48] Furthermore, we have reported that genetically obese leptin-(Lep) and leptin High fat diet and MT latency MP Cleary et al receptor-(Lepr) deficient mice crossbred with MMTV-TGF-a mice did not develop MTs. 24,25 Although we did not determine serum leptin levels in the present study, it has been reported that serum leptin levels were highest in obesity-prone rats compared to obesity-resistant and control rats, while obesity-resistant rats had higher leptin levels than the control rats.…”

Section: Discussionmentioning

confidence: 99%

Effect of high fat diet on body weight and mammary tumor latency in MMTV-TGF-α mice

2004

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OBJECTIVE:The role of high fat diets in breast cancer/mammary tumor (MT) development is controversial. This may be partially attributable to variable effects of high fat diets on body weight. Here, we used a moderately high fat diet (32.5% fat calories) expected to cause obesity in most mice, but predicted to result in some mice remaining in the weight range of mice fed the low fat diet (11% fat calories). This provided the opportunity to compare mice fed the high fat diet exhibiting different body weights and mice of similar weight consuming high vs low fat diets. EXPERIMENTAL METHODS: Transgenic MMTV-TGF-a mice, a model of postmenopausal breast cancer, consumed a low fat diet, that is, chow-fed (n ¼ 25) or a moderately high fat diet from 10 weeks of age (n ¼ 51). Body weight at 34 weeks of age was used to assign high fat diet mice to obesity-prone4overweight4obesity-resistant groups (n ¼ 17) (Po0.0001). Mice were euthanized when MTs developed or at 85 weeks of age. RESULTS: Final body weights were highest in obesity-prone4overweight 4obesity-resistant ¼ chow-fed mice. Fat pads and fat pad:carcass were heaviest in obesity-prone followed by overweight mice. However, obesity-resistant mice had fat pad weights and fat pad:carcass three-fold greater than chow-fed mice. All groups had MT incidences between 72 and 82%. Obesity-prone mice exhibited the shortest MT latency (Po0.0001), but obesity-resistant mice had significantly shorter latency than chow-fed mice. CONCLUSIONS: Consumption of a high fat diet increased adiposity and shortened MT latency in relation to its effect on body weight. These results indicate a complex role of dietary fat level on mammary tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Effect of high fat diet on body weight and mammary tumor latency in MMTV-TGF-α mice

2004

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“…[6][7][8] Interestingly, overexpression of the leptin system in breast cancer appears to be associated with higher tumor grade and size. [9][10][11][12][13] The mechanisms of leptin overexpression in breast cancer cells is partially known, for instance, we have shown that leptin transcription and synthesis can be induced by hypoxia or high levels of insulin. 9,13,14 Here we investigated whether leptin expression in breast cancer cells could be related to the existence of the Lep-2548G/A polymorphism in the promoter region of leptin gene.…”

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

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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

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“…Since leptin increased HBcec sensitivity to Z, it is possible that Z affected obese breast cancer patients more than cancer patients of average weight. Thus, the prognosis for obese breast cancer patients is worse, since more breast cancer patients exhibit leptin expression (9). Moreover, our MTT assay demonstrated that primary cultured HBcecs are more sensitive to leptin and Z than McF-7 adr cells (39).…”

Section: Discussionmentioning

confidence: 94%

“…Since leptin was found to be associated with several types of cancer (9), researchers attempted to find the relationship and mechanisms of leptin action in prostate cancer (10), gastric cancer (11), oral cancer (12), esophageal adenocarcinoma (13), hepatocellular carcinoma (14), gallbladder cancer (15) and breast cancer (16)(17)(18)(19)(20)(21)(22). ishikawa et al found that leptin was overexpressed in breast cancer cells (23) and concluded that high leptin levels in obese breast cancer patients may play a role in the development of antiestrogen resistance (21,23).…”

Section: Introductionmentioning

confidence: 99%

“…leptin is not expressed in normal breast tissue, but exists near malignant breast lesions (8), while its receptors were detectable in breast cancer cells, but undetectable in normal mammary epithelial cells (23). in addition to its mitogenic effects, leptin promotes the proliferation of the human breast cancer cell line T47-d (9). a high level of leptin may contribute to the development of a more aggressive malignant phenotype (24).…”

Section: Introductionmentioning

confidence: 99%

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Zeranol enhances leptin-induced proliferation in primary cultured human breast cancer epithelial cells

2010

Mol Med Rep

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Abstract. Breast cancer is the leading type of cancer in women in the united States. one of the known risk factors of breast cancer is obesity. leptin is a product of the obese (ob) gene and plays an important role in breast cancer development. its expression is up-regulated in obesity and it promotes breast cancer cell growth. exposure to environmental estrogenic disruptors has been found to be directly related to the increase in the incidence of breast cancer. Zeranol (Z) is a non-steroidal anabolic growth promoter with potent estrogenic activity that is widely used in the uS beef industry. The objective of this study was to determine the mechanisms of Z-and leptininduced proliferation of primary cultured human breast cancer epithelial cells (HBcecs). a cell proliferation assay was used to determine the extent to which Z is capable of enhancing the mitogenic activity of leptin in HBcecs. rT-Pcr was used to explore the possible mechanisms by quantifying the transcription of cyclin d1 and obr genes. our results demonstrated that when the HBcecs were pre-treated with 3 nM leptin for 24 h, the sensitivity to Z exposure greatly enhanced the mitogenic action of leptin. The experimental data observed show that there is interaction between leptin and Z in HBcec growth.

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Identification of leptin receptors in human breast cancer: functional activity in the T47-D breast cancer cell line

Cited by 177 publications

References 33 publications

Effect of high fat diet on body weight and mammary tumor latency in MMTV-TGF-α mice

Effect of high fat diet on body weight and mammary tumor latency in MMTV-TGF-α mice

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

Zeranol enhances leptin-induced proliferation in primary cultured human breast cancer epithelial cells

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