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Inhibitors of differentiation-1 promotes nitrosopyrrolidine-induced transformation of HPV 16-immortalized cervical epithelial cell.

Xie L, Li J, Zhang Y, Liu B, Peng X, Lin Y, Xu W, Hu L - Cancer Sci. (2014)

Bottom Line: Our previous study implied a correlation between inhibitors of differentiation-1 (Id-1) and cervical cancer development.However, how Id-1 contributes to cervical carcinogenesis is unknown.Our results suggest that Id-1 plays an oncogenic role in HPV-related cervical carcinogenesis, which sheds light on cervical cancer development mechanisms and implies that Id-1 is a potential target for cervical cancer prevention and therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, China; Laboratory of Biomedical Ultrasonics/Gynecological Oncology Laboratory, West China Second Hospital, Sichuan University, Chengdu, China.

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HE staining xenografted tumors in nude mice. (a) Tumors from N-nitrosopyrrolidine (NPYR) transformed pWPI H8 cells showed squamous cell carcionoma (SCC) with a better differentiation. (b) Tumors from NPYR transformed pWPI-hId H8 cells showed SCC with undifferentiated or low-grade differentiated type. (c) Tumors formed by SiHa cells showed SCC with undifferentiated type. Representative images (100× and 400× for the inserts) are shown.
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fig06: HE staining xenografted tumors in nude mice. (a) Tumors from N-nitrosopyrrolidine (NPYR) transformed pWPI H8 cells showed squamous cell carcionoma (SCC) with a better differentiation. (b) Tumors from NPYR transformed pWPI-hId H8 cells showed SCC with undifferentiated or low-grade differentiated type. (c) Tumors formed by SiHa cells showed SCC with undifferentiated type. Representative images (100× and 400× for the inserts) are shown.

Mentions: To determine whether Id-1 expression is required for transformation of H8 cells, we ectopically expressed Id-1 in H8 cells through lentivirus transduction. The stable Id-1-overexpressed H8 cells were sorted and purified using the BD FACSAria Flow Cytometer. Effective expression of Id-1 in pWPI-hId1-transduced cells was confirmed by western blot (Fig.4A). The cells were exposed to NPYR using our established protocol. As a result, H8 cells with a stable transduction of pWPI-hId1 showed an increased colony formation ability compared to the control plasmid pWPI (colony numbers: 75.4 ± 12.2 vs 48.4 ± 7.5, P < 0.05, Fig.4B,C). The results strongly support a promoting role of Id-1 in cervical epithelial cell transformation. We further investigated the biological consequence of Id-1 activation in tumorigenesis with the nude mouse xenograft model. pWPI-hId1 H8 cells developed larger tumors compared to the pWPI controls at the end of experiments (tumor size for pWPI-hId1 group: 1044 ± 142 mm3; control group: 427 ± 52 mm3, P < 0.05, Fig.5). Pathological analysis revealed that all the xenograft tumors were similar to human squamous cell carcinoma (SCC). However, tumors derived from Id1-overexpression cells (pWPI-hId-transfected) showed SCC with undifferentiated or low-grade differentiated types, while those from control cells (pWPI-transfected) revealed a better differentiation (Fig.6).


Inhibitors of differentiation-1 promotes nitrosopyrrolidine-induced transformation of HPV 16-immortalized cervical epithelial cell.

Xie L, Li J, Zhang Y, Liu B, Peng X, Lin Y, Xu W, Hu L - Cancer Sci. (2014)

HE staining xenografted tumors in nude mice. (a) Tumors from N-nitrosopyrrolidine (NPYR) transformed pWPI H8 cells showed squamous cell carcionoma (SCC) with a better differentiation. (b) Tumors from NPYR transformed pWPI-hId H8 cells showed SCC with undifferentiated or low-grade differentiated type. (c) Tumors formed by SiHa cells showed SCC with undifferentiated type. Representative images (100× and 400× for the inserts) are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317834&req=5

fig06: HE staining xenografted tumors in nude mice. (a) Tumors from N-nitrosopyrrolidine (NPYR) transformed pWPI H8 cells showed squamous cell carcionoma (SCC) with a better differentiation. (b) Tumors from NPYR transformed pWPI-hId H8 cells showed SCC with undifferentiated or low-grade differentiated type. (c) Tumors formed by SiHa cells showed SCC with undifferentiated type. Representative images (100× and 400× for the inserts) are shown.
Mentions: To determine whether Id-1 expression is required for transformation of H8 cells, we ectopically expressed Id-1 in H8 cells through lentivirus transduction. The stable Id-1-overexpressed H8 cells were sorted and purified using the BD FACSAria Flow Cytometer. Effective expression of Id-1 in pWPI-hId1-transduced cells was confirmed by western blot (Fig.4A). The cells were exposed to NPYR using our established protocol. As a result, H8 cells with a stable transduction of pWPI-hId1 showed an increased colony formation ability compared to the control plasmid pWPI (colony numbers: 75.4 ± 12.2 vs 48.4 ± 7.5, P < 0.05, Fig.4B,C). The results strongly support a promoting role of Id-1 in cervical epithelial cell transformation. We further investigated the biological consequence of Id-1 activation in tumorigenesis with the nude mouse xenograft model. pWPI-hId1 H8 cells developed larger tumors compared to the pWPI controls at the end of experiments (tumor size for pWPI-hId1 group: 1044 ± 142 mm3; control group: 427 ± 52 mm3, P < 0.05, Fig.5). Pathological analysis revealed that all the xenograft tumors were similar to human squamous cell carcinoma (SCC). However, tumors derived from Id1-overexpression cells (pWPI-hId-transfected) showed SCC with undifferentiated or low-grade differentiated types, while those from control cells (pWPI-transfected) revealed a better differentiation (Fig.6).

Bottom Line: Our previous study implied a correlation between inhibitors of differentiation-1 (Id-1) and cervical cancer development.However, how Id-1 contributes to cervical carcinogenesis is unknown.Our results suggest that Id-1 plays an oncogenic role in HPV-related cervical carcinogenesis, which sheds light on cervical cancer development mechanisms and implies that Id-1 is a potential target for cervical cancer prevention and therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, China; Laboratory of Biomedical Ultrasonics/Gynecological Oncology Laboratory, West China Second Hospital, Sichuan University, Chengdu, China.

Show MeSH
Related in: MedlinePlus