Leptin increases the expression of tumour promoter genes and decreases the expression of tumour suppressor genes in stomach of female Sprague-Dawley rats
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Faizatul Isyraqiah1,*,
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Methil Kannan Kutty2 and
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Harbindar Jeet Singh3,4
Author information
Department of Physiology, Faculty of Medicine, Melaka Manipal Melaka College, Melaka, Malaysia
Faculty of Medicine, University of Lincoln, Petaling Jaya, Selangor, Malaysia
Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Sg Buloh, Selangor, Malaysia
I-PPerFORM, Universiti Teknologi MARA, Malaysia
Correspondence to: Faizatul Isyraqiah, Department of Physiology, Faculty of Medicine, Melaka Manipal Melaka College, Melaka, Malaysia. E-mail:
faizatul.muhammad@manipal.edu.my
Abstract
Background
Epidemiologic studies indicate that the incidence of gastric cancer is lower in females than in males. However, a few reports have found no difference in the relative risk of gastric cancer in obese females compared to obese males. Our recent studies found that leptin promotes tumor growth in the stomach of male Sprague-Dawley rats. It is, however, unknown if leptin can also equally induce gastric tumorigenesis in female rats. This study therefore examined the effects of leptin on tumor development in stomachs of female Sprague-Dawley rats.
Methodology
Female Sprague-Dawley rats aged 6 weeks were divided into 2 groups; leptin group that was given
daily intraperitoneal injections of leptin at a dose of 60 µg/kg for 40 weeks (n=8) and a control group that was
given daily intraperitoneal injections of an equal volume of normal saline (n=8). Body weights were measured
weekly. After 40 weeks, the rats were euthanised and their stomachs collected for histopathological examination
and gene analysis. Nine target genes commonly involved in tumorigenesis were selected for RT-PCR, which
included APC, ARID1A, E-Cadherin, FAT4, L-Myc, PGC, PPARG, TFF1, and TFF2. Data were analysed using
one-way ANOVA.
Results
No macroscopic or microscopic changes were found in the stomach of leptin-treated rats. However, gene
analysis revealed significant decrease in tumour suppressor genes like ARID1A, E-cadherin, APC, TFF1, and
PPARG, but not FAT4. Tumour promoter genes L-Myc and TFF2 were both significantly upregulated in
leptin-treated rats. In situ expression of PGC, which is a negative marker for gastric cancer, was found decreased
considerably as well. No significant differences in body weight were found between control and leptin-treated rats.
Conclusion
The evident down regulation of some tumour suppressor genes and up-regulation of some tumour
promoter genes in leptin-treated rats seem to indicate a tumorigenic potential of leptin in female rats as well,
although it may not be as profound as reported in male Sprague-Dawley rats.
Keywords
leptin,
gastric cancer,
tumour suppressor,
tumour promoter
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Copyright © 2025 Authors.
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Isyraqiah F, Kutty MK, Singh HJ. Leptin increases the expression of tumour promoter genes and decreases the expression of tumour suppressor genes in stomach of female Sprague-Dawley rats. Gastroenterol & Hepatol Res. 2021;3(1):3. doi: 10.53388/ghr2021-03-029.
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Article History
| Received |
Revised |
Accepted |
Published |
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March 12, 2021
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DOI
http://dx.doi.org/10.53388/ghr2021-03-029
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Gastroenterology & Hepatology Research
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eISSN 2703-173X