BACKGROUND:The traditional view that immunoglobulin (Ig) is produced only by B lymphocytes has been challenged, because it has been demonstrated that Ig genes and proteins are expressed in epithelial cancer cells. However, whether Ig expression in nonlymphoid cells is limited to epithelial cells is unclear. Because sarcomas differ distinctly from carcinomas in their biologic and clinical features, the authors investigated the question of nonlymphoid IgG expression in soft tissue lesions. METHODS: Immunohistochemistry, in situ hybridization, and polymerase chain reaction (PCR) were used to demonstrate IgG expression in 80 soft tissue lesions. The correlation between Ig expression and proliferation markers (proliferating cell nuclear antigen [PCNA], Ki-67, and cyclin D1) in sarcomas was investigated by immunohistochemical and statistical analyses. RESULTS: Igj was identified in 97.4% of sarcomas and in 31.7% of benign lesions by immunohistochemistry. The difference was statistically significant (P < .01). Messenger RNA from the IgG1 heavy-chain constant region was also detected by in situ hybridization. Variable-diversity-joining recombination sequences of both heavy and light chains were obtained by PCR and sequencing. Moreover, the labeling index of PCNA, Ki-67, and cyclin D1 was much higher in sarcomas with high Igj expression than in sarcomas with low Igj expression (P < .01 for PCNA and cyclin D1; P < .001 for Ki-67). There were more grade 3 sarcomas with high Igj expression compared with grade 1 and 2 sarcomas (P < .05). CONCLUSIONS: IgG was identified in a wide variety of soft tissue tumors and correlated well with proliferation markers and tumor grades. IgG may be a useful marker for cell proliferation in sarcomas.
Background:
Cervical cancer (CC) is a prevalent gynecological carcinoma, and patients infected with human papillomavirus (HPV) have a higher morbidity rate.
Aims:
To explore the effects of ETS-like transcription factor 4 (ELK4) in patients with HPV
+
CC.
Study design:
In vitro cell lines and human-sample study.
Methods:
The ELK4 levels in human tissue (65 HPV
+
CC tissue and 25 HPV
−
normal cervical tissue) and cell lines (human cervical epithelial immortalized cell line H8 and CC cell lines HeLa [HPV18], CaSki [HPV16], and SiHa [HPV
−
]) were quantified using qRT-PCR and western blot assay. ELK4 knockdown transfection was effective and confirmed by western blotting. The MTT and EDU assays were used to evaluate cell viability and proliferation, respectively. Flow cytometry was used to detect the CC cell cycle stage. Stem cell markers, such as cluster of differentiation 133 (CD133), CD44, and aldehyde dehydrogenase 1, and the cervicospheres formed were measured. ChIP-qPCR and luciferase activity experiments were used to assess the bond between ELK4 and F-box protein 22 (FBXO22).
Results:
ELK4 was highly expressed in the HPV+ CC tissue. CC cells with ELK4 knockdown had lower viability and proliferation than the control cells. ELK4 knockdown blocked the progression of the cell cycle from G1 to S phase. ELK4 knockdown suppressed the stem cell-like characteristics of the HPV+ CC cells. ELK4 bonded with the FBXO22 promoter, inhibiting the levels of phosphatase and tensin homolog (PTEN).
Conclusion:
ELK4 facilitated cell cycle progression and stem cell-like characteristics by regulating the FBXO22/PTEN axis. Thus, ELK4 could be a potential therapeutic target to arrest the progress of HPV-associated CC.
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