Prolactin and Prolactin Receptor Expression in Cervical Intraepithelial Neoplasia and Cancer

Ascencio-Cedillo, Rafael; López-Pulido, Edgar Iván; Muñoz‐Valle, José Francisco; Villegas‐Sepúlveda, Nicolás; Toro-Arreola, Susana del; Estrada-Chávez, Ciro; Daneri-Navarro, ́Adrián; Franco-Topete, Ramón Antonio; Pérez-Montiel, Delia; García‐Carrancá, Alejandro; Pereira‐Suárez, Ana Laura

doi:10.1007/s12253-014-9814-6

Cited by 22 publications

(24 citation statements)

References 29 publications

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“…The molecular heterogeneity of PRL has been previously described (46), and we have provided evidence that the cell lines and tissues of cervical cancer synthesize a 60 kDa PRL variant, unlike the non-tumorigenic keratinocytes (HaCaT) that do not express this isoform (23,40). This PRL variant has been previously detected in PBMCs from patients with SLE and THP1 monocytes (25,32).…”

Section: Discussionsupporting

confidence: 61%

“…Persistent high-risk human papillomavirus infection is the main risk factor for cervical cancer; however, there are other important cofactors for this outcome. Previous results of our group show that a long PRLR isoform is mainly expressed in cervical cancer tissues (40), and its overexpression is associated to cell survival by inhibition of apoptosis (23). Moreover, we found the presence of a 60 kDa PRL isoform that is present in cervical cancer cells (23).…”

Section: Introductionsupporting

confidence: 64%

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A 60 kDa prolactin variant secreted by cervical cancer cells modulates apoptosis and cytokine production

et al. 2018

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Abstract. Prolactin (PRL) is associated with different types of cancer, such as cervical cancer. Recombinant PRL has antiapoptotic effect on cervical cancer cells, and it can also induce cytokine production on macrophages. A 60 kDa variant of PRL is produced by cervical cancer cells. The aim of the present study was to evaluate this variant's bioactivity, to test its effect on cervical cancer cell apoptosis, and to assess its ability to induce cytokine production on THP-1 macrophages. First, 60 kDa PRL was isolated and used to stimulate Nb2 cells. Later, apoptosis was measured after exposure to 60 kDa PRL. Finally, cytokines were measured on THP-1 stimulated supernatants. Our results show that 60 kDa PRL increased Nb2 cell proliferation. Apoptosis was decreased after stimuli with 60 kDa PRL in cervical cancer cells. IL-1β and TNF-α are produced by THP-1 macrophages after stimuli. These results suggest that 60 kDa PRL produced by cervical cancer cells is able to reduce apoptosis in HeLa, SiHa and C-33A cells and induce IL-1β and TNF-α production by THP-1 macrophages.

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Section: Discussionsupporting

confidence: 61%

Section: Introductionsupporting

confidence: 64%

A 60 kDa prolactin variant secreted by cervical cancer cells modulates apoptosis and cytokine production

et al. 2018

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“…It has previously been reported that PRLR expression is significantly increased in UCC compared with in normal tissue and precursor lesions (19). The internalization of PRLR and its translocation to the nucleus has been the subject of intense debate, due to conflicting results (44).…”

Section: Discussionmentioning

confidence: 99%

“…The signaling complex of prolactin (PRL) and PRL receptor (PRLR), using both endocrine and local paracrine/autocrine pathways, has also been implicated in the pathology of UCC (18)(19)(20). Initial studies analyzed the association between PRL/PRLR and the signaling pathways involved in proliferation and apoptosis of UCC cell lines.…”

Section: Effects Of 60 Kda Prolactin and Estradiol On Metabolism And mentioning

confidence: 99%

“…Initial studies analyzed the association between PRL/PRLR and the signaling pathways involved in proliferation and apoptosis of UCC cell lines. The expression levels of both PRL and PRLR were revealed to be increased in the cell lines, and are associated with cell survival; in addition, treatment with 200 ng/ml human recombinant PRL (hPRL) exerts a protective effect against etoposide-induced apoptosis (18,19). It has also been revealed that activation of signal transducer and activator of transcription 3 (STAT3) is required for the anti-apoptotic effects of hPRL (20), and PRLR expression is increased in histopathological samples of patients with UCC compared with in normal cervical tissues (20).…”

Section: Effects Of 60 Kda Prolactin and Estradiol On Metabolism And mentioning

confidence: 99%

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Effects of 60�kDa prolactin and estradiol on metabolism and cell survival in cervical cancer: Co‑expression of their hormonal receptors during cancer progression

et al. 2018

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Estrogens and estrogen receptors (ERs), such as ERα and ERβ, prolactin (PRL) and prolactin receptor (PRLR) have been reported to be involved in the physiopathology of uterine cervical cancer (UCC). The 60 kDa PRL is an isoform of PRL, which is produced by UCC-derived cells. The present study aimed to evaluate the expression of hormonal receptors in different degrees of cervical lesions, and to determine whether 60 kDa PRL and 17β-estradiol (E2) modulated cell survival and metabolism in UCC cells, and in HaCaT cells transduced with human papillomavirus (HPV) 16 and 18 E6/E7 oncogenes. ERα, ERβ, PRLR, Ki67 and B-cell lymphoma 2 expression levels were analyzed in biopsies of precursor lesions and UCC using immunohistochemistry. In addition, HeLa, SiHa and C33A cells, and transduced HaCaT cells, were stimulated with 60 kDa PRL, E2 or a combination of both. Proliferation was evaluated using the xCELLigence platform, apoptosis was analyzed by flow cytometry and cell metabolism was determined using the MTT assay. The results revealed that ERα, ERβ, PRLR and Ki67 expression levels were increased during the progression of cancer. In vitro, 60 kDa PRL alone significantly increased proliferation of SiHa cells. Furthermore, E2 alone or in combination with 60 kDa PRL increased the sensitivity of SiHa cells to cisplatin and increased the percentage of apoptosis; in HaCaT cells, these treatment strategies had the opposite effect on cisplatin sensitivity. Treatment with E2 increased mitochondrial activity in HeLa and SiHa cells, and in HaCaT cells transduced with HPV 16 E6/E7 and HPV 18 E6 oncogenes. PRL had a similar effect on HeLa cells, and on HaCaT cells transduced with HPV 18 E6 and HPV 16 E7. The co-expression of these receptors demonstrated the hormonal dependence of UCC. In addition, E2 and the 60 kDa PRL significantly impacted the metabolism, but not the survival, of cells.

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4SC-202 exerts an anti-tumor effect in cervical cancer by targeting PRLR signaling pathway

Zhang¹,

Li²,

Sun³

et al. 2022

J Mol Histol

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The aim of the present study is to investigate whether 4SC-202, a selective class I histone deacetylase inhibitor (HDACi), plays an anti-tumor role in cervical cancer (CC) by targeting prolactin receptor (PRLR). CCK-8 and colony formation assays were used to evaluate the effects of 4SC-202 on the proliferation of CC cells in vitro. Effects of 4SC-202 on the cell cycle distribution and apoptosis in SiHa cells were determined by ow cytometry and western blotting, respectively. Immuno uorescence and western blotting were performed to detect the activities of PRLR-related pathways and PRLR expression in CC cells. A xenograft tumor model in nude mice was established to examine effects of 4SC-202 on the tumor growth, apoptosis and PRLR-related pathways in vivo. The biochemical analyzer and H&E staining were used to detect the serum biochemical indexes and organ toxicity. 4SC-202 inhibited the proliferation of CC cells (SiHa, HeLa, and CaSki) in vitro in a time-and dose-dependent manner. SiHa cells were treated with 1 or 5 μM 4SC-202 for 72 h and then subjected to various functional assays. The assays showed that 4SC-202 signi cantly induced G2/M phase arrest and apoptosis, while inhibiting the activities of PRLR-related pathways and PRLR expression. In addition, 4SC-202 reduced tumor growth and induced apoptosis in vivo. 4SC-202 down-regulated the expression of PRLR and activities of PRLR-related pathways in the mouse model, displayed no effects on serum biochemical indicators and caused no toxicity to mouse organs. This nding suggests that 4SC-202 may serve as a novel therapeutic agent for CC.

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Prolactin and Prolactin Receptor Expression in Cervical Intraepithelial Neoplasia and Cancer

Cited by 22 publications

References 29 publications

A 60 kDa prolactin variant secreted by cervical cancer cells modulates apoptosis and cytokine production

A 60 kDa prolactin variant secreted by cervical cancer cells modulates apoptosis and cytokine production

Effects of 60�kDa prolactin and estradiol on metabolism and cell survival in cervical cancer: Co‑expression of their hormonal receptors during cancer progression

4SC-202 exerts an anti-tumor effect in cervical cancer by targeting PRLR signaling pathway

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