Epidermal Growth Factor Receptor Expression and the Presence of Human Papillomavirus in Cervical Squamous Intraepithelial Lesions

Chapman, William; Lörincz, Attila T.; Willett, Gerald; Wright, V. Cecil; Rj, Kurman

doi:10.1097/00004347-199207000-00009

Cited by 25 publications

(16 citation statements)

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“…The expression of growth factor receptor is also increased in cervical cancer tissues and cancer cells. EGF Receptor (EGFR) is related to HPV infection as EGFR cytoplasmic expression increases with increasing grade of CIN [22]. IGF-1 receptor (IGF-1R) expression level is elevated in cervical cancer cell cultures [23].…”

Section: Discussionmentioning

confidence: 99%

Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer

et al. 2014

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BackgroundThe apoptosis inhibitor-5 (API5), anti-apoptosis protein, is considered a key molecule in the tumor progression and malignant phenotype of tumor cells. Here, we investigated API5 expression in cervical cancer, its clinical significance, and its relationship with phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2) in development and progression of cervical cancer.MethodsAPI5 effects on cell growth were assessed in cervical cancer cell lines. API5 and pERK1/2 immunohistochemical staining were performed on a cervical cancer tissue microarray consisting of 173 primary cervical cancers, 306 cervical intraepithelial neoplasias (CINs), and 429 matched normal tissues.ResultsAPI5 overexpression promoted cell proliferation and colony formation in CaSki cells, whereas API5 knockdown inhibited the both properties in HeLa cells. Immunohistochemical staining showed that API5 expression increased during the normal to tumor transition of cervical carcinoma (P < 0.001), and this increased expression was significantly associated with tumor stage (P = 0.004), tumor grade (P < 0.001), and chemo-radiation response (P = 0.004). API5 expression levels were positively associated with pERK1/2 in cervical cancer (P < 0.001) and high grade CIN (P = 0.031). In multivariate analysis, API5+ (P = 0.039) and combined API5+/pERK1/2+ (P = 0.032) were independent prognostic factors for overall survival.ConclusionsAPI5 expression is associated with pERK1/2 in a subset of cervical cancer patients and its expression predicts poor overall survival, supporting that API5 may be a promising novel target for therapeutic interventions.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-545) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer

et al. 2014

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“…ras activation stimulates expression of HPV-16 E6/E7 RNAs after transient transfection into HeLa cells by increasing activity of AP-1 transcription factors [52]. Endogenous ras is activated through EGF-R signaling, and the EGF-R is often overexpressed in cervical carcinomas [53]. ras is also activated by the HPV E5 gene product [54].…”

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confidence: 99%

Tumor necrosis factor-? promotes human papillomavirus (HPV) E6/E7 RNA expression and cyclin-dependent kinase activity in HPV-immortalized keratinocytes by aras-dependent pathway

et al. 2000

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Tumor necrosis factor-alpha (TNF-alpha) inhibits growth of normal cervical keratinocytes but stimulates proliferation of human papillomavirus (HPV)-immortalized and cervical carcinoma-derived cell lines when mitogens such as epidermal growth factor (EGF) or serum are depleted. Current work identifies the mechanism of growth stimulation. TNF-alpha promoted cell cycle progression by increasing expression of HPV-16 E6/E7 RNAs and enhancing activity of cyclin-dependent kinase (cdk)2 and cdc2 after 3 d. Increased kinase activity was mediated by upregulation of cyclins A and B and decreases in cdk inhibitors p21(waf) and p27(kip). TNF-alpha stimulated these changes in part by increasing transcription and stabilization of RNA for amphiregulin, an EGF receptor ligand, and amphiregulin directly increased HPV-16 E6/E7 and cyclin A RNAs. To define which components of the EGF receptor signaling pathway were important, HPV-immortalized cells were transfected with activated or dominant negative mutants of Ha-ras, raf, or MAPKK. Expression of activated Ha-ras maintained HPV-16 and cyclin gene expression and promoted rapid growth in the absence of EGF. Furthermore, ras activation was necessary for TNF-alpha mitogenesis as transfection with a dominant negative ras mutant (Asn-17) strongly inhibited growth. Thus, activation of ras promotes expression of HPV-16 E6/E7 RNAs, induces cyclins A and B, and mediates growth stimulation of immortal keratinocytes by TNF-alpha. These studies define a pathway by which ras mutations, which occur in a subset of cervical cancers, may contribute to pathogenesis. Mol. Carcinog. 27:97-109, 2000. Published by Wiley-Liss, Inc.

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“…The EGFR is overexpressed or constitutively activated in many types of human cancer, including cervical carcinoma (7,8), and overexpression has been associated with a poor prognosis (7). EGFR activation can be inhibited using antibodies (9,10) or small molecule tyrosine kinase inhibitors (11), and inhibition of EGFR function has been shown to decrease growth of several types of human cancer in preclinical studies (12,13).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the epidermal growth factor receptor increases expression of genes that stimulate inflammation, apoptosis, and cell attachment

Woodworth

Michael²,

Marker³

et al. 2005

Molecular Cancer Therapeutics

105

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The epidermal growth factor receptor (EGFR) is overexpressed in several types of human cancer, and inhibition of EGFR function is a promising strategy for cancer therapy. We used cDNA microarrays to examine alterations in gene expression after treatment of carcinoma cells with PD153035, a specific and reversible inhibitor of EGFR function. When human cervical carcinoma cells were grown on a collagen substrate in three-dimensional organotypic culture, untreated cells expressed high levels of EGFR RNA and invaded the underlying collagen. Blocking EGFR function decreased DNA synthesis and inhibited invasion in a dose-dependent manner. Microarray analyses identified 312 genes that were significantly increased or decreased in expression after EGFR inhibition. Many could be classified into one of four functional groups including genes that (a) stimulate inflammation and innate immunity, (b) promote cell attachment, (c) enhance apoptosis, and (d) inhibit cell cycle progression. PD153035 induced a dose-dependent activation of nuclear factor KB, a transcription factor that stimulates proinflammatory gene expression. Our results identify alterations in gene expression caused by EGFR inhibition and show that this response varies significantly in different cell lines. [Mol Cancer Ther 2005;4(4):650 -8]

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Epidermal Growth Factor Receptor Expression and the Presence of Human Papillomavirus in Cervical Squamous Intraepithelial Lesions

Cited by 25 publications

References 0 publications

Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer

Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer

Tumor necrosis factor-? promotes human papillomavirus (HPV) E6/E7 RNA expression and cyclin-dependent kinase activity in HPV-immortalized keratinocytes by aras-dependent pathway

Inhibition of the epidermal growth factor receptor increases expression of genes that stimulate inflammation, apoptosis, and cell attachment

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