Leptin: A proliferative factor for breast cancer?

Caldefie-Chézet, Florence; Damez, Mireille; Latour, M. De; Końska, Grażyna; Mishellani, F.; Fusillier, C; Guerry, M; Penault‐Llorca, Frédérique; Guillot, Jean; Vasson, Marie‐Paule

doi:10.1016/j.bbrc.2005.06.077

Cited by 64 publications

(51 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Leptin is shown to be overexpressed in ductal breast tumors, contributing to a proliferative effect, while it is unexpressed in healthy breast tissue not in the vicinity of tumor growth [35]. The role of leptin in tumor growth is demonstrated via mice cancer models.…”

Section: Leptinmentioning

confidence: 99%

Adipose tissue, obesity and adipokines: role in cancer promotion

Booth

Magnuson

Fouts

et al. 2015

Hormone Molecular Biology and Clinical Investigation

252

235

View full text Add to dashboard Cite

Adipose tissue is a complex organ with endocrine, metabolic and immune regulatory roles. Adipose depots have been characterized to release several adipocytokines that work locally in an autocrine and paracrine fashion or peripherally in an endocrine fashion. Adipocyte hypertrophy and excessive adipose tissue accumulation, as occurs during obesity, dysregulates the microenvironment within adipose depots and systemically alters peripheral tissue metabolism. The term "adiposopathy" is used to describe this promotion of pathogenic adipocytes and associated adipose -elated disorders. Numerous epidemiological studies confirm an association between obesity and various cancer forms. Proposed mechanisms that link obesity/adiposity to high cancer risk and mortality include, but are not limited to, obesity-related insulin resistance, hyperinsulinemia, sustained hyperglycemia, glucose intolerance, oxidative stress, inflammation and/or adipocktokine production. Several epidemiological studies have demonstrated a relationship between specific circulating adipocytokines and cancer risk. The aim of this review is to define the function, in normal weight and obesity states, of wellcharacterized and novel adipokines including leptin, adiponectin, apelin, visfatin, resistin, chemerin, omentin, nesfatin and vaspin and summarize the data that relates their dysfunction, whether associated or direct effects, to specific cancer outcomes. Overall research suggests most adipokines promote cancer cell progression via enhancement of cell proliferation and migration, inflammation and anti-apoptosis pathways, which subsequently can prompt cancer metastasis. Further research and longitudinal studies are needed to define the specific independent and additive roles of adipokines in cancer progression and reoccurrence.

show abstract

Section: Leptinmentioning

confidence: 99%

Adipose tissue, obesity and adipokines: role in cancer promotion

Booth

Magnuson

Fouts

et al. 2015

Hormone Molecular Biology and Clinical Investigation

252

235

View full text Add to dashboard Cite

show abstract

“…Korner et al (2007) reported that AdipoR1 and AdipoR2 proteins were detected in 30.4 and 26.3% of breast cancer biopsies respectively. In previous studies, we demonstrated that leptin and leptin receptor (Ob-Rt) were involved in breast cancer, since both markers were expressed in mammary tumor (Caldefie-Chezet et al 2005, Jarde et al 2008a.…”

Section: Introductionmentioning

confidence: 99%

Involvement of adiponectin and leptin in breast cancer: clinical and in vitro studies

Jardé

Caldefie-Chézet

Goncalves-Mendès

et al. 2009

Endocrine-Related Cancer

136

121

View full text Add to dashboard Cite

Obesity is a risk factor for breast cancer development. A recent hypothesis suggests that the adipokines, adiponectin and leptin, are involved in breast cancer development. This prompted us to investigate the role of adiponectin and leptin in mammary carcinogenesis. Adiponectin receptors (AdipoR1 and AdipoR2) and leptin receptor (Ob-Rt, representing all the isoforms of Ob-R) proteins were detected by immunohistochemistry in in situ ductal carcinoma, invasive ductal malignancy, and healthy adjacent tissue. In addition, mRNA expression of adiponectin, AdipoR1, AdipoR2, leptin, Ob-Rt, and Ob-Rl (the long isoform of Ob-R) was observed in MCF-7 breast cancer cells. Interestingly, leptin mRNA expression was 34.7-fold higher than adiponectin mRNA expression in the MCF-7 cell line. Moreover, adiponectin (10 mg/ml) tended to decrease the mRNA expression of leptin (K36%) and Ob-Rl (K28%) and significantly decreased Ob-Rt mRNA level (K26%). In contrast, leptin treatment (1 mg/ml) significantly decreased AdipoR1 mRNA (K23%). Adiponectin treatment (10 mg/ml) inhibited the proliferation of MCF-7 cells, whereas leptin (1 mg/ml) stimulated the growth of cancer cells. In addition, adiponectin inhibited leptin-induced cell proliferation (both 1 mg/ml). Using microarray analysis, we found that adiponectin reduced the mRNA levels of genes involved in cell cycle regulation (mitogen-activated protein kinase 3 and ATM), apoptosis (BAG1, BAG3, and TP53), and potential diagnosis/prognosis markers (ACADS, CYP19A1, DEGS1, and EVL), whereas leptin induced progesterone receptor mRNA expression.In conclusion, the current study indicates an interaction of leptin-and adiponectin-signaling pathways in MCF-7 cancer cells whose proliferation is stimulated by leptin and suppressed by adiponectin.

show abstract

“…High expression of leptin and the long/signaling form of leptin receptor have been found in breast tumors (7)(8)(9)(10)(11). Leptin-deficient mice have decreased incidence of oncogeneinduced mammary tumors (12).…”

Section: Introductionmentioning

confidence: 99%

Programmed cell death 4 inhibits leptin-induced breast cancer cell invasion

et al. 2011

View full text Add to dashboard Cite

Abstract. Obesity is a significant risk factor for post-menopausal women to develop and die from breast cancer. Leptin, an adipokine is produced in high levels in obese individuals, and its receptor is overexpressed in breast tumors and lymph node metastases. Previously, we demonstrated that leptin stimulates breast cancer cell invasion, which is correlated with breast cancer metastasis. Programmed cell death 4 (PDCD4) has been shown to block cancer cell invasion. However, whether PDCD4 blocks leptin-induced breast cancer cell invasion is not known. Here, we report the novel findings that leptin failed to induce invasion in MCF-7 breast cancer cells overexpressing PDCD4 (MCF-7/PDCD4). Tissue inhibitor of metalloproteinase-2 (TIMP-2) was essential to the anti-invasive effect of PDCD4, as leptin stimulated the invasion of MCF-7/ PDCD4 cells pretreated with TIMP-2 siRNA. Furthermore, TIMP-2 knockdown allowed leptin to augment phosphorylation of extracellular signal-regulated kinases 1,2 and signal transducer and activator of transcription 3, but not that of Jun N-terminal kinases. These data indicate that PDCD4 utilizes TIMP-2 to exert its anti-invasive effect by suppressing leptininduced activation of extracellular signal-regulated kinases 1,2 and signal transducer and activator of transcription 3. Novel therapeutic strategies aiming at enhancing PDCD4 expression in breast tumors may be able to stop obesity-related breast tumor progression and prolong the life of patients. IntroductionBreast cancer is the most frequently diagnosed cancer in women. In 2010, about 207,090 new cases of invasive breast cancer were expected to be diagnosed among women, and about 39,840 women were expected to die from breast cancer. One of the major risk factors for postmenopausal women to develop breast cancer is obesity. Tumors from breast cancer patients with high body mass index are typically of the hormoneresponsive type (1-3). Leptin, a 16-kDa hormone that was discovered as a regulator of body weight and energy balance acting in the hypothalamus (4), is an important hormonal link between obesity and breast cancer. As body weight and fat mass increase, the level of circulating leptin increases (5,6).High expression of leptin and the long/signaling form of leptin receptor have been found in breast tumors (7-11). Leptin-deficient mice have decreased incidence of oncogeneinduced mammary tumors (12). An inhibitor targeted to the leptin receptor suppresses breast tumor formation in vivo (13). High levels of leptin in breast tumors have been correlated with poorer patient prognosis and increased incidence of metastasis (7,10,11). Breast cancer metastasis is directly associated with breast cancer cell invasion. Recently, we showed that leptin stimulates invasion of MCF-7 breast cancer cells by activating Jun N-terminal kinases (JNK), which increase matrix metalloproteinase-2 activity (14).Leptin has also been associated with the development of anti-estrogen resistance. Leptin is a potent modulator of the estrogen receptor signaling pathwa...

show abstract

Leptin: A proliferative factor for breast cancer?

Cited by 64 publications

References 34 publications

Adipose tissue, obesity and adipokines: role in cancer promotion

Adipose tissue, obesity and adipokines: role in cancer promotion

Involvement of adiponectin and leptin in breast cancer: clinical and in vitro studies

Programmed cell death 4 inhibits leptin-induced breast cancer cell invasion

Contact Info

Product

Resources

About