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Interaction between 17β-estradiol, prolactin and human papillomavirus induce E6/E7 transcript and modulate the expression and localization of hormonal receptors

  • Ramírez-López, Inocencia Guadalupe1, 2
  • Ramírez de Arellano, Adrián3
  • Jave-Suárez, Luis Felipe4
  • Hernández-Silva, Christian David1, 2
  • García-Chagollan, Mariel3
  • Hernández-Bello, Jorge3
  • Lopez-Pulido, Edgar I.5
  • Macias-Barragan, José6
  • Montoya-Buelna, Margarita2
  • Muñoz-Valle, José Francisco3
  • Pereira-Suárez, Ana Laura2, 3
  • 1 Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico , Guadalajara (Mexico)
  • 2 Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Laboratorio de Inmunología, Departamento de Fisiología, Sierra Mojada # 950, Colonia Independencia, Guadalajara, Jalisco, CP 44340, Mexico , Guadalajara (Mexico)
  • 3 Centro Universitario de Ciencias de La Salud, Universidad de Guadalajara, Instituto de Investigación en Ciencias Biomédicas, Guadalajara, Jalisco, Mexico , Guadalajara (Mexico)
  • 4 Instituto Mexicano del Seguro Social (IMSS), División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Sierra Mojada 800, Col. Independencia, Guadalajara, JAL, 44340, Mexico , Guadalajara (Mexico)
  • 5 Centro Universitario de Los Altos, Tepatitlán de Morelos, Universidad de Guadalajara, Departamento de Clínicas, Guadalajara, Jalisco, Mexico , Guadalajara (Mexico)
  • 6 Universidad de Guadalajara, Departamento de Ciencias de La Salud CUValles, Guadalajara- Ameca Rd Km. 45.5, Ameca, Jalisco, Mexico , Ameca (Mexico)
Published Article
Cancer Cell International
Springer (Biomed Central Ltd.)
Publication Date
Sep 02, 2019
DOI: 10.1186/s12935-019-0935-6
Springer Nature


BackgroundCervical cancer (CC) is the second most common cancer in less developed countries and the second leading cause of death by cancer in women worldwide. The 99% of CC patients are infected with the Human Papilloma Virus (HPV), being HPV16 and HPV18 infection the most frequent. Even though HPV is considered to be a necessary factor for the development of CC, it is not enough, as it requires the participation of other factors such as the hormonal ones. Several studies have demonstrated the requirement of estrogen and its receptors (ERα, ERβ, and GPER) in the precursor lesions progress towards CC. Also, prolactin (PRL) and its receptor (PRLR) have been associated with CC. The molecular mechanisms underlying the cooperation of these hormones with the viral oncoproteins are not well elucidated. For this reason, this study focused on analyzing the contribution of 17β-estradiol (E2), PRL, and HPV on the expression and localization of hormone receptors, as well as to evaluate whether these hormones may promote greater expression of HPV oncogenes and contribute to tumor progression.MethodsqPCR was used to evaluate the effect of E2 and PRL on the expression of E6 and E7 oncoproteins in HeLa and SiHa cervical cancer cells lines. HaCaT cells were transduced with the viral oncogenes E6 and E7 from HPV 16 and 18. ERα, ERβ, GPER, and PRLR expression and localization were evaluated by qPCR, Western blot and immunofluorescence.ResultsE2 and PRL induce E6/E7 oncogenes expression in HeLa and SiHa cells. E6 and E7 oncogenes of HPV16/18 significantly increased the protein expression of ERα, GPER, and PRLR. ERβ was positively regulated only by E6 oncogenes of HPV16/18. Besides, some of these oncogenes modify the location of PRLR toward cytoplasm, and ERα, ERβ, and GPER mainly to the nucleus.ConclusionOur studies suggest that the mutual regulation between E2, PRL, and HPV oncogenes could cooperate with the carcinogenesis process in CC.

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