The Possible Role of p53 and bcl-2 Expression in Cervical Carcinomas and Their Premalignant Lesions

Dimitrakakis, Constantine; Kymionis, George D.; Diakomanolis, Emmanuel; Papaspyrou, Irene; Rodolakis, A; Arzimanoglou, Iordanis; Leandros, Emmanuel; Michalas, S.

doi:10.1006/gyno.1999.5715

Cited by 63 publications

(47 citation statements)

References 28 publications

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“…Overexpression of Bcl-2 is closely related to multiple epithelial tumors resulting from DNA damage and continued survival and subsequently aggregated mutations. Furthermore, the presence of the Bcl-2 protein is strongly associated with the development of invasive cervical disease (25) and Bcl-2 was significantly correlated to the grades of cervical intraepithelial neoplasia (26). The apoptotic effect of miR-29 is Mcl-1-and Bcl-2-dependent (27).…”

Section: Discussionmentioning

confidence: 99%

miR-143 is downregulated in cervical cancer and promotes apoptosis and inhibits tumor formation by targeting Bcl-2

Liu

Guo

et al. 2011

Mol Med Report

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Section: Discussionmentioning

confidence: 99%

miR-143 is downregulated in cervical cancer and promotes apoptosis and inhibits tumor formation by targeting Bcl-2

Liu

Guo

et al. 2011

Mol Med Report

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“…In contrast, miR-143 through the regulation of antiapoptotic Bcl-2 may play an important role in the pathogenesis of CC as tumor suppressor; overexpression of miR-143 in HeLa cells results in apoptosis and suppression of both Bcl-2 expression and cell proliferation (27). Furthermore, the presence of the Bcl-2 protein is strongly associated with the development of CC (28) and was significantly correlated to the grades of cervical intraepithelial neoplasia (29).…”

Section: Introductionmentioning

confidence: 99%

The expression of miR-21 and miR-143 is deregulated by the HPV16 E7 oncoprotein and 17β-estradiol

Gómez‐Gómez

Organista‐Nava

Ocadiz-Delgado

et al. 2016

International Journal of Oncology

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Abstract. MicroRNAs (miRNAs) are a class of non-coding RNAs that negatively regulate their target mRNAs at a posttranscriptional level, thereby affecting crucial processes in cancer development. However, little is known about the molecular events that control expression of miRNAs in cervical cancer (CC). HPV16 E7 oncoprotein in conjunction with estrogen are sufficient to produce high grade cervical dysplasia and invasive cervical malignancies in a mouse model. In the present study, we determined the potential role that the E7 oncoprotein and 17β-estradiol (E 2 ) play in the deregulation of miR-21 and miR-143 expression levels by these two risk factors. We found that, while the expression of miR-21 was upregulated and the expression of miR-143 was downregulated by the HPV16 E7 oncoprotein in vivo, and in vitro and that E 2 treatment is also implicated in the deregulation of these important miRNAs in vivo. Sustained upregulation of miR-21 resulted in suppression of PTEN expression, and repression of miR-143 increased the mRNA and protein levels from Bcl-2. These results suggested that HPV type 16 E7 oncoprotein and E 2 play an important role in regulating miR-21 and miR-143 expression. We have observed similar results in CC patients containing HPV16 sequences, suggesting that these miRNAs could serve as diagnostic biomarkers in CC. The present study highlights the roles of miRNAs in cervical tissue and implicates these important molecules in cervical carcinogenesis.

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“…An overexpression of Bcl-2 and Bcl-X L proteins has been noted in cervical carcinoma-derived cell lines (Liang et al, 1995;Yang et al, 1999). Evaluation of Bcl-2 expression may even provide additional prognostic information for the clinical course of cervical disease, Bcl-2 expression increasing with the grade of pre-malignant lesions (Dimitrakakis et al, 2000). Bcl-2 and Bcl-X L prevent the opening of permeability transition pore complex (PTPC) and, consequently, cell death by hindering the mitochondrial permeability transition and cytochrome c release (Newmeyer et al, 2000), whereas the proapoptotic Bax or Bak, after insertion and oligomerization into the outer mitochondrial membrane, triggers cytochrome c release (Crompton, 2000;Makin et al, 2001;Manon et al, 1997;Narita et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Human papillomaviruses type 16+ and 18+ cervical carcinoma cells are sensitive to staurosporine‐mediated apoptosis

Bernard¹,

Prétet²,

Charlot³

et al. 2003

Biology of the Cell

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We have recently shown that staurosporine (ST) can trigger apoptosis of CaSki and HeLa cervical tumor cells from G2/M checkpoint, though the mechanism remains elusive. In this study, we reported that ST induced the inhibition of E6 and E7 viral oncogene and MDM2 expression, while it led to increased levels of p53, which was transiently located to mitochondria. Additionally, the proteins of the p53-regulated genes, p21 WAF1 and Bax, were increased with a similar time, while Bcl-2 and Bcl-X L expression was lowered. Upon ST treatment, the cytochrome c was released into the cytosol and, then, activation of caspases-9 and -3 led to Poly(ADP)RibosePolymerase (PARP) cleavage. Finally, characteristic morphological signs confirmed the apoptosis execution. Thus, taken together, all these observations suggest that apoptosis can be reactivated in HPV-positive human carcinoma cells and highlight that ST could be used as a potently chemotherapy agent to enhance the sensitivity of tumor cells to apoptosis.

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The Possible Role of p53 and bcl-2 Expression in Cervical Carcinomas and Their Premalignant Lesions

Cited by 63 publications

References 28 publications

miR-143 is downregulated in cervical cancer and promotes apoptosis and inhibits tumor formation by targeting Bcl-2

miR-143 is downregulated in cervical cancer and promotes apoptosis and inhibits tumor formation by targeting Bcl-2

The expression of miR-21 and miR-143 is deregulated by the HPV16 E7 oncoprotein and 17β-estradiol

Human papillomaviruses type 16+ and 18+ cervical carcinoma cells are sensitive to staurosporine‐mediated apoptosis

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