Expression of Cell Cycle-related Proteins p16, p27 and Ki-67 Proliferating Marker in Laryngeal Squamous Cell Carcinomas and in Laryngeal Papillomas

Ciesielska, Urszula; Zatoński, Tomasz; Nowińska, Katarzyna; Ratajczak‐Wielgomas, Katarzyna; Grzegrzółka, Jędrzej; Piotrowska, Aleksandra; Olbromski, Mateusz; Puła, Bartosz; Podhorska-Okołów, Marzena; Dzięgiel, Piotr

doi:10.21873/anticanres.11580

Cited by 23 publications

(25 citation statements)

References 23 publications

(45 reference statements)

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“…VSMCs proliferation is a complex and stepwise process, which is regulated by various cell cycle proteins including p27, PCNA and Ki‐67. Among them, p27 could suppress cell cycle progress through arresting cells in the G0/G1 phase, while PCNA and Ki‐67 was closely related to DNA synthesis and cell mitosis respectively . We next conducted double immunofluorescent staining with antibodies against (PCNA, Ki‐67 and p27) and α‐smooth muscle actin (α‐SMA), a marker for smooth muscle cells.…”

Section: Resultsmentioning

confidence: 99%

Aberrant MFN2 transcription facilitates homocysteine‐induced VSMCs proliferation via the increased binding of c‐Myc to DNMT1 in atherosclerosis

Hao

et al. 2019

J Cellular Molecular Medi

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It is well‐established that homocysteine (Hcy) is an independent risk factor for atherosclerosis. Hcy can promote vascular smooth muscle cell (VSMC) proliferation, it plays a key role in neointimal formation and thus contribute to arteriosclerosis. However, the molecular mechanism on VSMCs proliferation underlying atherosclerosis is not well elucidated. Mitofusin‐2 (MFN2) is an important transmembrane GTPase in the mitochondrial outer membrane and it can block cells in the G0/G1 stage of the cell cycle. To investigate the contribution of aberrant MFN2 transcription in Hcy‐induced VSMCs proliferation and the underlying mechanisms. Cell cycle analysis revealed a decreased proportion of VSMCs in G0/G1 and an increased proportion in S phase in atherosclerotic plaque of APOE −/− mice with hyperhomocystinaemia (HHcy) as well as in VSMCs exposed to Hcy in vitro. The DNA methylation level of MFN2 promoter was obviously increased in VSMCs treated with Hcy, leading to suppressed promoter activity and low expression of MFN2. In addition, we found that the expression of c‐Myc was increased in atherosclerotic plaque and VSMCs treated with Hcy. Further study showed that c‐Myc indirectly regulates MFN2 expression is duo to the binding of c‐Myc to DNMT1 promoter up‐regulates DNMT1 expression leading to DNA hypermethylation of MFN2 promoter, thereby inhibits MFN2 expression in VSMCs treated with Hcy. In conclusion, our study demonstrated that Hcy‐induced hypermethylation of MFN2 promoter inhibits the transcription of MFN2, leading to VSMCs proliferation in plaque formation, and the increased binding of c‐Myc to DNMT1 promoter is a new and relevant molecular mechanism.

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Section: Resultsmentioning

confidence: 99%

Aberrant MFN2 transcription facilitates homocysteine‐induced VSMCs proliferation via the increased binding of c‐Myc to DNMT1 in atherosclerosis

Hao

et al. 2019

J Cellular Molecular Medi

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“…It is a non-histone protein present in the nucleus of dividing cells (20). In LSCC, the increase in the Ki-67 proliferation index is associated with progression and greater tumour aggressiveness (8,21,22). To the best of our knowledge, this is the first study examining the relationship of Metallothionein I and II (MT-I/II) with MCM5 in LSCC.…”

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confidence: 89%

MCM5 Expression Is Associated With the Grade of Malignancy and Ki-67 Antigen in LSCC

et al. 2019

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Background/Aim: The minichromosome maintenance proteins (MCMs) may be potential biomarkers of cancer cell proliferation. They are essential to initiate DNA replication. The aim of the study was to investigate the level of MCM5 expression in benign lesions (BLs) and laryngeal squamous cell cancer (LSCC). Materials and Methods: Immunohistochemical (IHC) analysis was carried out on 83 LSCCs and 10 BLs. Western-blot, immunofluorescence analysis (IF) and real-time PCR (RT-PCR) were performed using HEp-2 cancer cells and HaCaT keratinocytes. Results: The expression of MCM5 was higher in LSCC than in the BLs (p<0.0001) and was higher in subsequent malignancies of LSCC. Positive correlations were demonstrated between the expression levels of MCM5 and the Ki-67 antigen. In vitro studies have confirmed that the expression of MCM5 is elevated in cancer cells. Conclusion: MCM5 protein may be used as a potential marker of cancer cell proliferation in LSCC.

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“…In fact, it was hypothesized that cytoplasmic staining represents the cellular mechanism in which p16 becomes inactivated and allows for tumor progression [51,52]. Cytoplasmic p16 has been studied as a potential prognostic marker in squamous cell carcinoma of the head and neck, with increased survival correlating with higher cytoplasmic staining [53][54][55]. Both the functional role of oncogenic cellular senescence in vaginal squamous cell carcinoma development and the mechanistic role of Arid1a in the translocation of p16 need further investigation.…”

Section: Arid1a Knockdown Repressed Oncogenic-induced Cellular Senescmentioning

confidence: 99%

Vaginal squamous cell carcinoma develops in mice with Arid1a loss and gain of oncogenic Kras

Wang

Praça

Wendel

et al. 2020

Preprint

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Recent sequencing studies showed that loss-of-function mutations in ARID1A (AT-rich interactive domain 1a) were enriched in gynecologic malignancies. However, multiple mouse models with deletion of Arid1a did not exhibit gynecologic malignancy. Oncogenic KRAS mutations are a common finding in endometrial cancers. However, expression of oncogenic Kras (KrasG12D) in the uterus was not sufficient to develop endometrial cancer. These results suggest that both ARID1A deletion and oncogenic KRAS require additional hits before driving gynecologic malignancy. To determine the role of the combination effects of deletion of Arid1a and oncogenic Kras, Arid1aflox/flox mice were crossed to KrasLox-Stop-Lox-G12D/+ mice using progesterone receptor Cre (PgrCre/+). Survival studies, histology, and immunohistochemistry were used to characterize the phenotype. Hormone dependence was evaluated by ovarian hormone depletion and estradiol replacement. Arid1aflox/flox; KrasLox-Stop-Lox-G12D/+; PgrCre/+ (AKP) mice exhibited early euthanasia due to large vaginal tumors, which were invasive squamous cell carcinoma. Younger mice exhibited precancerous intraepithelial lesions that progressed to invasive squamous cell carcinoma with age. Immunohistochemistry supported the pathological diagnosis with abnormal expression and localization of cytokeratin 5, tumor protein P63, cyclin dependent kinase inhibitor 2A (CDKN2A or p16), and marker of proliferation Ki-67. Vaginal lesions in AKP mice were hormone dependent. Ovarian hormone deletion in AKP mice resulted in atrophic vaginal epithelium without evidence of vaginal tumors. Estradiol replacement in ovarian hormone depleted AKP mice resulted in lesions that resembled the squamous cell carcinoma in intact mice. AKP mice did not develop endometrial cancer. Arid1a deletion with KrasG12D expression drives invasive vaginal squamous cell carcinoma. This mouse can be used to study the transition from benign precursor lesions into invasive vaginal squamous cell carcinoma offering insights into progression.

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Expression of Cell Cycle-related Proteins p16, p27 and Ki-67 Proliferating Marker in Laryngeal Squamous Cell Carcinomas and in Laryngeal Papillomas

Abstract: There is a necessity in finding biomarkers, which would predict the risk level of malignant transformation. Our study has confirmed that altered expressions of the p16 and p27 proteins might be useful biomarkers in the progression of laryngeal squamous cell carcinomas (LSCC).

Cited by 23 publications

References 23 publications

Aberrant MFN2 transcription facilitates homocysteine‐induced VSMCs proliferation via the increased binding of c‐Myc to DNMT1 in atherosclerosis

Aberrant MFN2 transcription facilitates homocysteine‐induced VSMCs proliferation via the increased binding of c‐Myc to DNMT1 in atherosclerosis

MCM5 Expression Is Associated With the Grade of Malignancy and Ki-67 Antigen in LSCC

Vaginal squamous cell carcinoma develops in mice with Arid1a loss and gain of oncogenic Kras

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