Expression of Leptin Receptors and Potential Effects of Leptin on the Cell Growth and Activation of Mitogen-Activated Protein Kinases in Ovarian Cancer Cells

Choi, Jung‐Hye; Park, Sehyung; Leung, Peter C.K.; Choi, Kyung‐Chul

doi:10.1210/jc.2004-0297

Cited by 106 publications

(97 citation statements)

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“…Previous reports have described a growth-stimulatory effect of leptin on gastric (Pai et al 2005), breast (Hu et al 2002, Stephenson & Rose 2003, Rose et al 2004, ovarian (Choi et al 2005) and prostate (Somasundar et al 2003) cancer cells. However, it inhibits the growth of pancreatic carcinoma (Somasundar et al 2003), suggesting a differential response of various cancer cells to leptin treatment.…”

Section: Discussionmentioning

confidence: 89%

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Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways

Sharma¹,

Saxena²,

Vertino³

et al. 2006

Endocr Relat Cancer

154

144

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An increase in the risk of cancer is one of the consequences of obesity. The predominant cancers associated with obesity have a hormonal basis and include breast, prostate, endometrium, colon and gall-bladder cancers. Leptin, the key player in the regulation of energy balance and body weight control also acts as a growth factor on certain organs in both normal and disease states. Therefore, it is plausible that leptin acts to promote cancer growth by acting as a mitogenic agent. However, a direct role for leptin in endometrial cancer has not been demonstrated. In this study, we analyzed the proliferative role of leptin and the mechanism(s) underlying this action in endometrial cancers which express both short and long isoforms of leptin receptors. Treatment with leptin resulted in increased proliferation of ECC1 and Ishikawa cells. The promotion of endometrial cancer cell proliferation by leptin involves activation of STAT3 and ERK2 signaling pathways. Moreover, leptin-induced phosphorylation of ERK2 and AKT was dependent on JAK/ STAT activation. Therefore blocking its action at the JAK/STAT level could be a rational therapeutic strategy for endometrial carcinoma in obese patients. We also found that leptin potently induces invasion of endometrial cancer cells in a Matrigel invasion assay. Leptinstimulated invasion was effectively blocked by pharmacological inhibitors of JAK/STAT (AG490) and phosphatidylinositol 3-kinase (LY294002). Taken together these data indicate that leptin promotes endometrial cancer growth and invasiveness and implicate the JAK/STAT and AKT pathways as critical mediators of leptin action. Our findings have potential clinical implications for endometrial cancer progression in obese patients.

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Section: Discussionmentioning

confidence: 89%

“…Both short and long isoforms of leptin receptors were observed in endometrial cancer cells, suggesting that leptin may be involved in endometrial cancer. In a recent report it was shown that not all ovarian cancer cell lines respond to leptin treatment, despite the presence of its receptors (Choi et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways

Sharma¹,

Saxena²,

Vertino³

et al. 2006

Endocr Relat Cancer

154

144

View full text Add to dashboard Cite

show abstract

“…Although leptin has been viewed as the hormonal signal for the regulation of energy homoeostasis (Auwerx and Staels, 1998), several lines of evidence suggest that leptin plays a much broader physiological role (Rosenbaum and Leibel, 1999;Zhang et al, 2005). On a cellular level, leptin has been found to act as a metabolic regulator and motogenic and pro-angiogenic factors (Sierra-Honignann et al, 1998;Hardwick et al, 2001;Hu et al, 2002;Chio et al, 2004;Yin et al, 2004;Chen et al, 2006a). In addition, new evidence suggests that leptin could be involved in tumorigenesis, especially in the development of breast, colorectal and prostate cancers .…”

Section: Discussionmentioning

confidence: 99%

Circulating levels of leptin, adiposity and breast cancer risk

et al. 2009

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The present case -control study was to investigate the relationships of plasma leptin level and anthropometric measures of adiposity with the risk of breast cancer. Questionnaire information, anthropometric measures and blood samples were taken before treatment from 297 incident cases with breast cancer and 593 controls admitted for health examination at the Tri-Service General Hospital, Taipei, between 2004 and. Plasma levels of leptin were measured by RIA. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for assessing the associations. Overall, higher leptin concentrations were significantly associated with an increased risk of breast cancer (OR (95% CI) for top vs bottom tertile of leptin was 1.63 (1.07 -2.49), P trend ¼ 0.009). Waist circumference was a significant anthropometric factor for breast cancer in both pre-and postmenopausal women. Furthermore, the associations of leptin with breast cancer risk remained after adjustment for obesity indices. These results suggest that leptin may have an independent role in breast tumorigenesis. Regardless of the impact of circulating leptin, more research is needed to elucidate molecular mechanisms and local leptin levels that are critical for the development of breast cancers. British Journal of Cancer (2009) Epidemiologic evidence suggested that obesity is associated with an increased risk of breast cancer in women, primarily in postmenopausal population (Calle and Thun, 2004). However, the molecular mechanisms underlying the obesity -breast cancer link are not fully clear. One important factor contributing to obesity -breast carcinogenesis might be an excess exposure of mammary epithelium to various bioactive substances produced by the adipose tissue (adipokines). Indeed, adipose tissue is a source of oestrogens, insulin and insulin-like growth factors, all of which are believed to be involved in mammary tumorigenesis (Schäffler et al, 2007). The most prominent adipokine is leptin, which is best known as a regulator of food intake and energy balance in the hypothalamus (Auwerx and Staels, 1998). Interestingly, leptin is also implicated in the regulation of reproductive hormones and function . Notably, leptin consistently stimulates the proliferation of benign and malignant epithelial breast cells in vitro as measured by DNA synthesis and upregulation of downstream regulators of cellular proliferation (Dieudonne et al, 2002;Hu et al, 2002). Thus, the intriguing possibility exists that leptin could be directly related to breast carcinogenesis by underlying the effects of obesity on cancer development. We have undertaken a case -control study to test this hypothesis. MATERIALS AND METHODS Case and control selectionThis case -control study was conducted at the Tri-Service General Hospital, Taipei, Taiwan, from January 2004 to November 2006. To account for the notions that type 2 diabetes and metabolic syndrome (MS) have been associated with increased serum leptin levels and elevated risk of breast cancer (Vona-D...

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“…Recent data clearly indicate that the mitogenic, anti-apoptotic, proinflammatory and angiogenic properties of leptin promote the development and progression of different types of cancers (9). Several reports have described the mitogenic effects of leptin on gastric (10), breast (11), ovarian (12), prostate (13) and endometrial cancer cells (14). Two studies demonstrated that increased leptin levels are associated with greater risk of CRC development, particularly in males (15,16).…”

Section: Introductionmentioning

confidence: 99%

Leptin-induced adhesion and invasion in colorectal cancer cell lines

et al. 2014

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Abstract. Leptin, which is encoded by the obese gene, is a multifunctional neuroendocrine peptide that regulates appetite, bone formation, reproductive function and angiogenesis. The aims of the present study were to investigate the expression of leptin in 80 patients with colorectal cancer (CRC) and to determine the effects of leptin on the malignant properties of CRC cells. We evaluated the expression of leptin in tissues of 80 patients with CRC. Suspension cultures were used to isolate CRC stem cells following pretreatment with leptin. We analyzed the effects of leptin on the adhesion and invasive capacities of CRC cell lines. The effects of leptin on JAK and ERK activation were examined using western blotting. Leptin expression was associated with CRC progression and increased the number and size of spheroid formation by CRC cell lines. Leptin enhanced cell invasion and adhesion and activated JAK and ERK signaling in the CRC cell lines. The present study demonstrated that leptin influences the growth and survival of CRC stem cells and regulates adhesion and invasion of colorectal carcinoma through activation of the JAK and ERK signaling pathways.

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Expression of Leptin Receptors and Potential Effects of Leptin on the Cell Growth and Activation of Mitogen-Activated Protein Kinases in Ovarian Cancer Cells

Cited by 106 publications

References 0 publications

Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways

Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways

Circulating levels of leptin, adiposity and breast cancer risk

Leptin-induced adhesion and invasion in colorectal cancer cell lines

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