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

  • Authors:
    • Annie Riera‑Leal
    • Adrián Ramírez De Arellano
    • Inocencia Guadalupe Ramírez‑López
    • Edgar I. Lopez‑Pulido
    • Judith R. Dávila Rodríguez
    • José G. Macías‑Barragan
    • Pablo César Ortiz‑Lazareno
    • Luis Felipe Jave‑Suárez
    • Cristina Artaza‑Irigaray
    • Susana Del Toro Arreola
    • Margarita Montoya‑Buelna
    • José Francisco Muñoz‑Valle
    • Ana Laura Pereira‑Suárez
  • View Affiliations

  • Published online on: September 28, 2018     https://doi.org/10.3892/or.2018.6743
  • Pages: 3781-3793
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Abstract

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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December-2018
Volume 40 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Riera‑Leal A, Ramírez De Arellano A, Ramírez‑López IG, Lopez‑Pulido EI, Dávila Rodríguez JR, Macías‑Barragan JG, Ortiz‑Lazareno PC, Jave‑Suárez LF, Artaza‑Irigaray C, Del Toro Arreola S, Del Toro Arreola S, et al: Effects of 60 kDa prolactin and estradiol on metabolism and cell survival in cervical cancer: Co‑expression of their hormonal receptors during cancer progression. Oncol Rep 40: 3781-3793, 2018
APA
Riera‑Leal, A., Ramírez De Arellano, A., Ramírez‑López, I.G., Lopez‑Pulido, E.I., Dávila Rodríguez, J.R., Macías‑Barragan, J.G. ... Pereira‑Suárez, A. (2018). Effects of 60 kDa prolactin and estradiol on metabolism and cell survival in cervical cancer: Co‑expression of their hormonal receptors during cancer progression. Oncology Reports, 40, 3781-3793. https://doi.org/10.3892/or.2018.6743
MLA
Riera‑Leal, A., Ramírez De Arellano, A., Ramírez‑López, I. G., Lopez‑Pulido, E. I., Dávila Rodríguez, J. R., Macías‑Barragan, J. G., Ortiz‑Lazareno, P. C., Jave‑Suárez, L. F., Artaza‑Irigaray, C., Del Toro Arreola, S., Montoya‑Buelna, M., Muñoz‑Valle, J. F., Pereira‑Suárez, A."Effects of 60 kDa prolactin and estradiol on metabolism and cell survival in cervical cancer: Co‑expression of their hormonal receptors during cancer progression". Oncology Reports 40.6 (2018): 3781-3793.
Chicago
Riera‑Leal, A., Ramírez De Arellano, A., Ramírez‑López, I. G., Lopez‑Pulido, E. I., Dávila Rodríguez, J. R., Macías‑Barragan, J. G., Ortiz‑Lazareno, P. C., Jave‑Suárez, L. F., Artaza‑Irigaray, C., Del Toro Arreola, S., Montoya‑Buelna, M., Muñoz‑Valle, J. F., Pereira‑Suárez, A."Effects of 60 kDa prolactin and estradiol on metabolism and cell survival in cervical cancer: Co‑expression of their hormonal receptors during cancer progression". Oncology Reports 40, no. 6 (2018): 3781-3793. https://doi.org/10.3892/or.2018.6743