Vitamin A deficiency in K14E7HPV expressing transgenic mice facilitates the formation of malignant cervical lesions
© 2021 Scandinavian Societies for Medical Microbiology and Pathology..
Infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer (CC), but viral infection alone does not guarantee the development of this malignancy. Indeed, deficiencies of dietary micronutrients could favor cervical cancer development in individuals that harbor HR-HPV infections. The status of retinoid levels, natural and synthetic derivatives of vitamin A, is important in maintaining cellular differentiation of the cervical epithelium. Moreover, many studies show a link between deficient intake of retinoids or alteration of the retinoid receptors and CC development. In spite of this, the effect of vitamin A deficiency (VAD) in presence of HR-HPV oncoproteins on cervical carcinogenesis in vivo has not been reported. Transgenic mice expressing E6 or E7 oncoproteins (K14E6 or K14E7 mice, respectively) were used to evaluate the possible role of VAD in the development of malignant cervical lesions. The survival of the mice in VAD condition was studied, and histopathological analysis and immunohistochemical detection of molecular cancer markers such as the tumor suppressor retinoic acid receptor beta (RARβ), proliferating cell nuclear antigen (PCNA), cleaved caspase 3, and the tumor suppressor protein p16INK4A (inhibitor of CDK4) were performed. Our results show that K14E6/VAD mice showed moderate cervical dysplasia; notably, K14E7/VAD mice developed severe cervical dysplasia and cervical in situ carcinoma at an early age. VAD synergizes with HPV16E7 oncoprotein expression favoring cervical carcinogenesis in vivo.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:129 |
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| Enthalten in: |
APMIS : acta pathologica, microbiologica, et immunologica Scandinavica - 129(2021), 8 vom: 30. Aug., Seite 512-523 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ocadiz-Delgado, Rodolfo [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.08.2021 Date Revised 23.08.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/apm.13159 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM325956758 |
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| 245 | 1 | 0 | |a Vitamin A deficiency in K14E7HPV expressing transgenic mice facilitates the formation of malignant cervical lesions |
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| 520 | |a © 2021 Scandinavian Societies for Medical Microbiology and Pathology. | ||
| 520 | |a Infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer (CC), but viral infection alone does not guarantee the development of this malignancy. Indeed, deficiencies of dietary micronutrients could favor cervical cancer development in individuals that harbor HR-HPV infections. The status of retinoid levels, natural and synthetic derivatives of vitamin A, is important in maintaining cellular differentiation of the cervical epithelium. Moreover, many studies show a link between deficient intake of retinoids or alteration of the retinoid receptors and CC development. In spite of this, the effect of vitamin A deficiency (VAD) in presence of HR-HPV oncoproteins on cervical carcinogenesis in vivo has not been reported. Transgenic mice expressing E6 or E7 oncoproteins (K14E6 or K14E7 mice, respectively) were used to evaluate the possible role of VAD in the development of malignant cervical lesions. The survival of the mice in VAD condition was studied, and histopathological analysis and immunohistochemical detection of molecular cancer markers such as the tumor suppressor retinoic acid receptor beta (RARβ), proliferating cell nuclear antigen (PCNA), cleaved caspase 3, and the tumor suppressor protein p16INK4A (inhibitor of CDK4) were performed. Our results show that K14E6/VAD mice showed moderate cervical dysplasia; notably, K14E7/VAD mice developed severe cervical dysplasia and cervical in situ carcinoma at an early age. VAD synergizes with HPV16E7 oncoprotein expression favoring cervical carcinogenesis in vivo | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a E7HPV oncogene | |
| 650 | 4 | |a HPV | |
| 650 | 4 | |a Vitamin A deficiency | |
| 650 | 4 | |a cervical cancer | |
| 650 | 7 | |a Cyclin-Dependent Kinase Inhibitor p16 |2 NLM | |
| 650 | 7 | |a Papillomavirus E7 Proteins |2 NLM | |
| 650 | 7 | |a Proliferating Cell Nuclear Antigen |2 NLM | |
| 650 | 7 | |a Receptors, Retinoic Acid |2 NLM | |
| 650 | 7 | |a oncogene protein E7, Human papillomavirus type 16 |2 NLM | |
| 650 | 7 | |a retinoic acid receptor beta |2 NLM | |
| 700 | 1 | |a Serafin-Higuera, Nicolás |e verfasserin |4 aut | |
| 700 | 1 | |a Alvarez-Rios, Elizabeth |e verfasserin |4 aut | |
| 700 | 1 | |a García-Villa, Enrique |e verfasserin |4 aut | |
| 700 | 1 | |a Tinajero-Rodríguez, Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Rodríguez-Uribe, Genaro |e verfasserin |4 aut | |
| 700 | 1 | |a Escobar-Wilches, Derly-Constanza |e verfasserin |4 aut | |
| 700 | 1 | |a Estela Albino-Sánchez, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Ramírez-Rosas, Alejandro |e verfasserin |4 aut | |
| 700 | 1 | |a Sierra-Santoyo, Adolfo |e verfasserin |4 aut | |
| 700 | 1 | |a Hernández-Pando, Rogelio |e verfasserin |4 aut | |
| 700 | 1 | |a Lambert, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Gariglio, Patricio |e verfasserin |4 aut | |
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