Association of Polymorphisms in the Genes of Angiotensinogen and Angiotensin Receptors With Risk for Basal Cell Carcinoma

Papaggelopoulos, John; Angelopoulou, Antonia; Avgoustidis, Dimitrios; Koronellos, Nikolas; Derka, Spyridoula; Vassiliou, Stavros; Yapijakis, Christos

doi:10.21873/anticanres.13745

“…8 Increased AGT gene expression was detected in two-fold increased frequency in basal cell carcinoma(BCC) patients in comparison to healthy controls,that could include that increased expression of AGT may be associated with BCC. 9 Our study similarly found that AGT may present a high expression in the lung metastasis microenvironment with breast cancer , while Wumei decoction can reduce AGT expression. A study showed that in the tumor microenvironment of renal cell carcinoma, cancer cells were activated by CCL20 secreted by tumor-associated macrophages through Akt activation, followed by epithelialmesenchymal transition and an acquired migration ability.…”

Section: Discussionsupporting

confidence: 68%

Effect of Wumei Decoction on Core Signal Transduction Molecules of Microenvironment in Lung Metastasis of Breast Cancer

wang

¹

,

Li

²

,

He

³

et al. 2020

Preprint

0

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Background The influence of traditional Chinese medicine on the tumor microenvironment is one of the mechanisms of its overall conditioning effect. In this study, we observed the influence of Wumei decoction,a traditional Chinese medicine classic prescription, on the core signal transduction molecules of the lung metastasis microenvironment in the model of lung metastasis of breast cancer in mice. Methods A breast cancer animal model established by inoculating the second pair of mammary fat pads of SPF grade Balb/c female mice with mouse breast cancer 4T1 cells, stably transduced luciferase. Model animals were divided into drug observation group, drug control group and blank control group. Bioluminescence imaging technique in vivo was used to observe the growth and metastasis of breast cancer in situ and lung. The gene expression in the lung metastasis microenvironment of the drug observation group and the blank control group was detected by Agilent expression profiling chip, and the differential genes were screened. And STRING (https://string-db.org/) online analysis system was used to obtain the signal transduction network, and then the MCODE plug-in of Cytosacpe software was used to obtain the core signal transduction molecule. Finally, the expression of these signal transduction molecules was detected by RT-PCR, immunohistochemistry and Western blot. Results Observed from the bioluminescence imaging technology in vivo, the fluorescent area of the breast cancer in inoculation area of each group mice gradually increased over time, indicating that the tumor volume is continuously increasing. The fluorescence distribution of the blank control group was dispersed on the 30th day, which had exceeded the vicinity of the original inoculation focus, indicating that the tumor had obvious metastasis. However, the drug observation group and the drug control group did not show such obvious transfer. Transcription expression profile chip results showed that there were 123 differentially expressed genes in the drug observation group and the blank control group, of which 64 genes were up-regulated and 59 genes were down-regulated. The signal transduction network of the 123 differentially expressed genes was obtained. The core genes recommended were AGT, CCL20, CXCL9, CXCL10, and HTR1B. RT-PCR results showed that the expression of AGT, CCL20, CXCL9, CXCL10, and HTR1B in the drug observation group were reduced compared with the blank control group, and the difference was statistically significant, p < 0.01. The results of immunohistochemistry showed that the core genes of the drug observation group showed a low expression trend, and the difference of CCL20 and CXCL10 was statistically significant, p < 0.01. Western blotting results also showed that each core gene protein in the drug observation group, compared with the blank control group, showed a downward trend. The difference of AGT and CCL20 was statistically significant, p < 0.01, and the difference of CXCL10 was also statistically significant, p < 0.05 . Conclusions Wumei decoction,a traditional Chinese medicine classic prescription, can inhibit lung metastasis of breast cancer to a certain extent. Inhibiting the expression of AGT, CCL20, CXCL9, CXCL10, HTR1B and other core signal transduction molecules in the lung metastasis microenvironment is one of its mechanisms.

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“…A two-fold increased expression of the Angiotensinogen gene in tumor cells of patients with BCC has been shown 9 . Although the role of the reninangiotensin system in the skin physiology is undeniable, 10 it remains unclear whether this expression is a result or a cause for the development of BCC.…”

Section: Discussionmentioning

confidence: 99%

Giant BCC of the scalp after telmisartan/amlodipine: potential role of nitrosamine contamination as main cause for skin cancer development

Tchernev¹,

Kordeva²

2024

PJDV

1

0

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The problem of drug-induced cancers, and in particular skin cancers after intake of various antihypertensive drugs, is increasing, but at the same time is gaining some clarity. In addition to melanocytic cancers, development of keratinocytic cancers is increased after the administration of sartans. It is believed that the procarcinogenic potential of the medication could be due to contamination of tablets with nitrosamines, which are known as mutagens. Regardless of the presence of angiotensin receptors in the skin and tumor tissue, the pharmacologic influence of the sartan is considered to be secondary and insignificant in relation to the processes of carcinogenesis. In certain cases, this influence is even defined as an antitumorous effect. We present a female patient who had been taking telmisartan/amlodipine 80/5 mg daily for 9 years and, after 4-5 years, developed a scalp tumor, confirmed histopathologically as a basal cell carcinoma (BCC) and treated successfully by surgical excision. The discussion is mainly focused on the potential role of nitrosamines as a new key player in the pathogenesis of keratinocytic cancers and BCC in particular.

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“…Altogether, 699 related studies were searched; at last, nine of them were included into the present meta-analysis according to the predetermined study inclusion and exclusion criteria [12][13][14][15][16][17][18][19][20]. All our collected articles were published from 2007 to 2020.…”

Section: Study Featuresmentioning

confidence: 99%

Associations between AGT M235T Polymorphism and Cancer: An Updated Meta-Analysis

Kou

¹

,

Huang

²

2022

J Renin Angiotensin Aldosterone Syst

0

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We assessed the relationship between AGT gene M235T polymorphism and the susceptibility to cancer by performing an updated meta-analysis. This study retrospectively searched related articles in the electronic databases. Afterwards, we determined combined odds ratios (ORs) and related 95% confidence intervals (CIs) by the fixed- or random-effects model. The present meta-analysis enrolled altogether 9 articles. On the whole, the relationship between AGT M235T polymorphism and the cancer risk was not significant among the entire population (TT vs. MM: OR = 1.28 , 95 % CI = 0.80 − 2.04 ; TM vs. MM: OR = 0.90 , 95 % CI = 0.53 − 1.52 ; recessive model: OR = 1.13 , 95 % CI = 0.83 − 1.52 ; dominant model: OR = 0.93 , 95 % CI = 0.55 − 1.57 ). Subgroup analysis by ethnicity, cancer type, and study quality for the relationship between the AGT M235T polymorphism and cancer risk showed no significant association. According to findings in the present meta-analysis, AGT M235T polymorphism may not be related to cancer susceptibility.

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Association of Polymorphisms in the Genes of Angiotensinogen and Angiotensin Receptors With Risk for Basal Cell Carcinoma

Cited by 13 publications

References 0 publications

Effect of Wumei Decoction on Core Signal Transduction Molecules of Microenvironment in Lung Metastasis of Breast Cancer

Effect of Wumei Decoction on Core Signal Transduction Molecules of Microenvironment in Lung Metastasis of Breast Cancer

Giant BCC of the scalp after telmisartan/amlodipine: potential role of nitrosamine contamination as main cause for skin cancer development

Associations between AGT M235T Polymorphism and Cancer: An Updated Meta-Analysis

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