In Vivo Tissue-Specific Regulation of the Human Papillomavirus Type 18 Early Promoter by Estrogen, Progesterone, and Their Antagonists

Morales-Peza, Néstor; Auewarakul, Prasert; Juarez, Victoria; García‐Carrancá, Alejandro; Cid-Arregui, Ángel

doi:10.1006/viro.2001.1287

Cited by 8 publications

(11 citation statements)

References 21 publications

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“…It has been proposed that epithelial ERα may also play a role in cervical carcinogenesis. Estrogen activates HPV promoter that drives E6/E7 expression in the cervical epithelium of HPV18URR-lacZ transgenic mice [44]. Enhanced expression of E6 and E7 provides selective growth advantage to cells [45].…”

Section: Discussionmentioning

confidence: 99%

Requirement for Stromal Estrogen Receptor Alpha in Cervical Neoplasia

et al. 2012

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The major etiological factor for cervical cancer is the high-risk human papillomavirus (HPV), which encodes E6 and E7 oncogenes. However, HPV is not sufficient and estrogen has been proposed as an etiological cofactor for the disease. Its requirement has been demonstrated in mouse models for HPV-associated cervical cancer (e.g., K14E7 transgenic mice). Although germline knockout of estrogen receptor alpha (ERα) renders mice resistant to cervical cancer, the cell type-specific requirement for ERα is not known. In this study, we demonstrate that temporal deletion of stromal ERα induced complete regression of cervical dysplasia in K14E7 mice. Our results strongly support the hypothesis that stromal ERα is necessary for HPV-induced cervical carcinogenesis and implicate paracrine mechanisms involving ERα signaling in the development of estrogen-dependent cervical cancers. This is the first evidence to support the importance of stromal ERα in estrogen-dependent neoplastic disease of the female reproductive tract.

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Section: Discussionmentioning

confidence: 99%

Requirement for Stromal Estrogen Receptor Alpha in Cervical Neoplasia

et al. 2012

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“…The tissue‐specific induction of the HPV‐18 early promoter in the genital epithelium of transgenic mice was suppressed by ovariectomy but restored by administration of estrogen alone or in combination with progesterone. Tamoxifen and RU486 reversed this latter effect 52. Squamous metaplasia appears to represent the first stage of transformation 46.…”

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confidence: 96%

Relationship between steroid hormone contraceptives and HPV, cervical intraepithelial neoplasia and cervical carcinoma

Villiers

2002

Intl Journal of Cancer

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Available data demonstrate an increase in the transcription of high-risk papillomaviruses by the 16␣-hydroxylation of estrogens, which is in line with the epidemiologic data showing an increased cervical carcinogenesis risk for long-term contraceptive-using, HPV-infected women. No evidence exists for an increase in HPV-negative contraceptive users. © 2002 Wiley-Liss, Inc. Key words: HPV; hormone; cervical intraepithelial neoplasia; cervical cancerInfection by papillomaviruses is essential for the development of cervical cancer (reviewed by zur Hausen 1 ). A number of the papillomavirus types (high-risk) have been associated with and demonstrated in premalignant and malignant lesions of the genital tract. The infection per se is, however, not sufficient to induce malignant conversion. A complex interplay between viral and cellular genes is required to disrupt the cell-cycle control and induce immortalization, followed by progression to malignant conversion. The molecular mechanism through which papillomaviruses, in particular HPV-16 and HPV-18, participate to achieve this condition has been well established. The low-risk mucosal papillomaviruses, causing benign lesions mainly of the genital tract, share several functional characteristics with the high-risk mucosal papillomaviruses but lack others necessary for the immortalization of normal keratinocytes (reviewed by zur Hausen 2 ). The maintenance of a high level of certain viral proteins within the cell is necessary for the virus to induce and regulate distinct cellular pathways. Several exogenous and endogenous factors controlling or influencing viral transcription and the expression of the viral oncogenes, E6 and E7 in particular, are known. Very few data are available on the in vitro and in vivo mechanisms through which steroid hormones, in particular, influence the carcinogenic process induced by high-risk papillomavirus infections.Steroid hormones exert a broad range of biologic functions. The synthesis, transport and metabolism of the naturally occurring hormones are tightly regulated in various organs of the body (reviewed by Clemens and Goss 3 and Gruber et al. 4 ). A delicate balance exists during the premenstrual, menstrual and postmenopausal phases of the female body, as well as during pregnancy. This balance is greatly influenced by the intake of exogenous steroid hormones in the form of OCs in young women or HRT in postmenopausal women. Reports in which epidemiologic data taken from 8 case-control studies have been pooled and analyzed indicate an increased risk for developing cervical carcinoma in women with high parity 5 or after the long-term use of OCs. 6 Odds ratios were 3.8 for cervical carcinoma after 7 full-term pregnancies, and 2.3 for women with 1 or 2 full-term pregnancies, respectively. Odds ratios for use of OCs were 2.82 for 5-to 9-year use and 4.03 for 10-year or longer use. Other epidemiologic studies have also reported an increased risk of developing cervical adenocarcinoma among long-term users of OCs. [7][8][9] Regulation of viral ...

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“…The LCR is known to drive HPV E6 and E7 transcription (GarciaCarranca et al 1988). In addition, LCR-dependent transcription is specifically repressed with oestrogen and progesterone antagonists, indicating that the LCR may contain responsive elements sensitive to oestrogens (Morales-Peza et al 2002). The strongest evidence for the role of oestrogen-ERα signalling in CC has been obtained from studies with HPV transgenic mice.…”

Section: In Vivo Studies Indicate the Requirement Of Oestrogens And Ersmentioning

confidence: 81%

Functional association of oestrogen receptors with HPV infection in cervical carcinogenesis

Ramachandran¹

2017

Endocrine-Related Cancer

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Repeated parity and usage of oral contraceptives have demonstrated an increased risk of cervical cancer (CC) in HPV-infected women. These lifestyle observations raise the likelihood that oestrogens and HPV infection might act synergistically to affect cancers of the cervix. In vivo studies have indicated the requirement of oestrogens and ERα in the development of atypical squamous metaplasia followed by cervical intraepithelial neoplasia (CIN) I, II and III. CIN II and III are precancerous cervical lesions that can progress over time to CC as an invasive carcinoma. Recently, there has been evidence suggesting that ERα signalling in the tumour epithelium is a preliminary requisite during cancer initiation that is subsequently lost during tumorigenic progression. Conversely, continued expression of stromal ERα gains control over tumour maintenance. This review summarises the current information on the association between oestrogens and HPV infection in contributing to CC and the possibility of SERMs as a therapeutic option.

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In Vivo Tissue-Specific Regulation of the Human Papillomavirus Type 18 Early Promoter by Estrogen, Progesterone, and Their Antagonists

Cited by 8 publications

References 21 publications

Requirement for Stromal Estrogen Receptor Alpha in Cervical Neoplasia

Requirement for Stromal Estrogen Receptor Alpha in Cervical Neoplasia

Relationship between steroid hormone contraceptives and HPV, cervical intraepithelial neoplasia and cervical carcinoma

Functional association of oestrogen receptors with HPV infection in cervical carcinogenesis

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