STAT3 activation is required for the antiapoptotic effects of prolactin in cervical cancer cells.
BACKGROUND
Prolactin (PRL) has been implicated in the development of different types of cancer. However, signaling pathways might be activated depending on various forms of prolactin receptor (PRLR). JAK/STAT is an important pathway associated with PRL effects. The activation of JAK/STAT pathway might activate antiapoptotic genes that could importantly lead to progression of tumorigenesis. Recently, we have reported that PRL is associated with cell survival by inhibition of apoptosis and the precise activated signaling pathways for this process are still questioned. The purpose of this study was to evaluate the activation of different signaling pathways in response to PRL as well as to identify the induction of antiapoptotic genes.


METHODS
Cervical cancer cell lines HeLa, SiHa and C-33 A were stimulated with PRL (200 ng/mL) for 30 and 60 min and non stimulated cells were used to measure basal protein expression. Inhibition assays were performed by using Jak2 specific inhibitor AG490, either alone or in combination with PRL for 48 h. Western blot were carried out to evaluate protein induction of the different signaling pathways and antiapoptotic proteins. Significant effects were determined by using ANOVA test.


RESULTS
STAT3 was significantly activated in cervical cancer lines in comparison with non-tumorigenic keratinocytes HaCaT. No significant differences were found when analyzing MAPK and PI3K signaling pathways. An increase of antiapoptotic genes Bcl-xl, Bcl-2, survivin and Mcl-1 was observed after stimulus with PRL; however, after inhibition with AG490, the induction of antiapoptotic genes was decreased.


CONCLUSIONS
Our data suggests that STAT3 is an important signaling pathway activated by PRL in cervical cancer cells and it modulates the induction of antiapoptotic genes. Blocking STAT3 could represent a possible therapeutic strategy in cervical cancer.
Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco Mexico ; Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada # 950, Colonia Independencia, 44340 Guadalajara, Jalisco Mexico.
Adrián
A
Ramírez de Arellano
Departamento de Clínicas, Centro Universitario de Los Altos, Tepatitlán de Morelos, Jalisco Mexico.
Edgar I
EI
Lopez-Pulido
Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco Mexico ; Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada # 950, Colonia Independencia, 44340 Guadalajara, Jalisco Mexico.
Priscila A
PA
Martínez-Neri
Unidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco A.C., 44270 Guadalajara, Jalisco Mexico.
Ciro
C
Estrada Chávez
Instituto Tecnológico y de Estudios Superiores de Monterrey, Campus Guadalajara, Zapopan, Jalisco Mexico.
Renee
R
González Lucano
Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada # 950, Colonia Independencia, 44340 Guadalajara, Jalisco Mexico.
Mary
M
Fafutis-Morris
Centro Médico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco Mexico.
A
A
Aguilar-Lemarroy
Centro Universitario de Ciencias de la Salud, Instituto de Investigación en Ciencias Biomédicas, Universidad de Guadalajara, Guadalajara, Jalisco Mexico.
José F
JF
Muñoz-Valle
Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada # 950, Colonia Independencia, 44340 Guadalajara, Jalisco Mexico.
Ana Laura
AL
Pereira-Suárez
Cervical cancer; PRL; STAT3