leptin and Uterine-Cervical-Dysplasia

Leptin may be involved in the pathogenesis of numerous cancer types by activation of cellular signal-transduction pathways. In this study, we analyzed the role of leptin and the mechanism(s) underlying its action in cervical carcinoma cells. Firstly, we examined the expression of leptin in 80 cases of cervical carcinoma using immunohistochemical staining. The results showed that the levels of leptin correlated significantly with the grades of cervical carcinoma. At the same time, the expression of leptin correlated positively with c-myc and its downstream gene, bcl-2. The expression of c-myc and bcl-2 was evaluated in leptin-treated HeLa cells by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. Recombinant leptin significantly activated the expression of bcl-2 and c-myc in HeLa cells. Finally, the apoptotic index, the proliferative activity and the expression levels of c-myc and bcl-2 were determined in the HeLa cells treated with silencing of leptin. We found that silencing of leptin inhibited the proliferation of HeLa cells and reduced the expression of bcl-2 and c-myc. Our data demonstrated that leptin interferes with the expression of oncogenic c-myc and anti-apoptotic bcl-2, and regulates cell turnover and facilitates the progression of cervical cancer.

Topics: Adult; Aged; Apoptosis; Carcinoma, Squamous Cell; Cell Proliferation; Female; Gene Expression; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Leptin; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-myc; RNA, Messenger; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Serum levels of vascular endothelial growth factor (VEGF) can be seen as surrogate markers of angiogenesis. Recently, leptin, which is involved in the control of satiety and energy expenditure, was also shown to modulate angiogenesis. As angiogenesis plays an abundant role in cervical carcinogenesis, we evaluated serum VEGF and leptin in patients with cervical intraepithelial neoplasia (CIN) and cervical cancer.. Serum VEGF and leptin were measured in 84 patients with cervical cancer, in 28 patients with CIN I-III, and in 35 healthy women, using a commercially available enzyme-linked immunosorbent assay and radioimmunoassay, respectively.. Serum VEGF was significantly elevated in patients with cervical cancer and in patients with CIN I-III compared to healthy women. In patients with cervical cancer serum VEGF was significantly correlated with tumor stage, but not with lymph node involvement and histological grade. Univariate and multivariate analyses showed that elevated pretreatment serum VEGF was not associated with the duration of disease-free and overall survival. Serum leptin did not differ among patients with cervical cancer, patients with CIN I-III, and healthy women. Serum leptin was significantly correlated with body mass index (BMI). All further analyses were performed with absolute and serum leptin corrected by BMI. No differences in serum leptin could be ascertained between patients with cervical cancer and patients with CIN I-III. Serum leptin was not associated with any clinicopathological parameter and patients' survival. No correlation between serum VEGF and leptin was found.. It can be speculated that serum VEGF might be used as a surrogate marker of angiogenesis in patients with cervical cancer. Our data support the concept that VEGF plays a role in malignant transformation and tumor growth, but not in the lymphatic spread of cervical cancer. This is the first report on leptin in a gynecological malignancy. Our results show that serum leptin falls short of being a useful marker in patients with cervical cancer.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease-Free Survival; Endothelial Growth Factors; Female; Humans; Leptin; Lymphokines; Middle Aged; Neoplasm Staging; Neovascularization, Pathologic; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors