Leptin stimulates ovarian cancer cell growth and inhibits apoptosis by increasing cyclin D1 and Mcl-1 expression via the activation of the MEK/ERK1/2 and PI3K/Akt signaling pathways
Authors: Mary Breslin
Chiachen Chen
Yuan-Ching Chang
Michael S Lan
Journal: International Journal of Oncology (2013)
Discipline: CLINICAL MEDICINE
Keywords: Obesity; Cancer; Leptin; Ovarian cancer; Growth

Abstract:  Obesity is known to be an important risk factor for many types of cancer, such as breast, prostate, liver and endometrial cancer. Recently, epidemiological studies have indicated that obesity correlates with an increased risk of developing ovarian cancer, the most lethal gynecological cancer in developed countries. Leptin is predominantly produced by adipocytes and acts as a growth factor and serum leptin levels positively correlate with the amount of body fat. In this study, we investigated the effects of leptin on the growth of ovarian cancer cells and the underlying mechanism(s) of action. Our results showed that leptin stimulated the growth of the OVCAR-3 ovarian cancer cell line using MTT assay and trypan blue exclusion. Using western blot analysis, we found that leptin enhanced the expression of cyclin D1 and Mcl-1, which are important regulators of cell proliferation and the inhibition of apoptosis. To investigate the signaling pathways that mediate the effects of leptin, cells were treated with leptin plus specific inhibitors of JAK2, PI3K/Akt and MEK/ERK1/2 and analysis of the phosphorylation state of proteins was carried out by western blot assays. We showed that the activation of the MEK/ERK1/2 and PI3K/Akt signaling pathways were involved in the growth-stimulating effect of leptin on ovarian cancer cell growth and the specific inhibitors of PI3K/Akt and MEK/ERK1/2 revealed that these two pathways interacted with each other. Our data demonstrate that leptin upregulates the expression of cyclin D1 and Mcl-1 to stimulate cell growth by activating the PI3K/Akt and MEK/ERK1/2 pathways in ovarian cancer. 

Retracted: No

PubPeer comments:
 June 2016 Corrigendum:  Following the publication of this article, an interested reader drew to our attention an anomaly associated with the presentation of Figs. 5 and 8; essentially, the u03b2-actin control bands in Fig. 8 appeared to be a mirror image of the same control bands shown in Fig. 5A. After having re-examined the data, Fig. 5 was correctly presented as shown in the paper, although the u03b2-actin blot in Fig. 8 had been inadvertently misplaced as a mirror image of the control data from Fig. 5. Two similar experiments were performed at that time, yielding similar results, and the error with the control data did not affect the second of the experiments. Therefore, we present a corrected version of Fig. 8 containing the alternative data. The findings and conclusions of this paper are still supported by our experimental data, and were not affected by this error. We sincerely apologize for this mistake, and thank the reader of our article who drew this matter to our attention. Furthermore, we regret any inconvenience this mistake has caused. Here are the original Figures 5 and 8. The beta-actin panels (marked in blue boxes) look identical to each other, if one of the figures is flipped horizontally. ![file] , 
 Of note, the  Corrected Figure 8, appears to be identical to the original Figure 8, with the offending beta-actin blot and the right-most lanes removed, and not the  alternative data , as suggested by the authors. Here is a comparison of the original and corrected version of Figure 8, marked with red boxes to draw attention to the similar-looking blot panels. ![file] , 
 The correction of Figure 8 does also not address an unexpected similarity between the Akt panels of Figure 5A and 8. Shown here in green, while the blue boxes highlight the same problem mentioned in comment #1. Could the authors please check this similarity as well? ![file] , 
 In addition, the re-used b-actin blot also looks very similar to a blot used in Figure 9A of a 2007 paper by shared authors, i.e. Chiachen Chen et al. Endocrine-Related Cancer (2007), DOI: 10.1677 ERC-06-0027. See: https: pubpeer.com publications 990D372692D43AA729FE9CB6C0C2D3 Here are all three potential instances of this blot next to each other: ![file] ,