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Open Access 01-12-2015 | Primary research

STAT3 activation is required for the antiapoptotic effects of prolactin in cervical cancer cells

Authors: Adrián Ramírez de Arellano, Edgar I. Lopez-Pulido, Priscila A. Martínez-Neri, Ciro Estrada Chávez, Renee González Lucano, Mary Fafutis-Morris, A. Aguilar-Lemarroy, José. F. Muñoz-Valle, Ana Laura Pereira-Suárez

Published in: Cancer Cell International | Issue 1/2015

Abstract

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.

Conclusion

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.

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Title: STAT3 activation is required for the antiapoptotic effects of prolactin in cervical cancer cells
Authors: Adrián Ramírez de Arellano
Edgar I. Lopez-Pulido
Priscila A. Martínez-Neri
Ciro Estrada Chávez
Renee González Lucano
Mary Fafutis-Morris
A. Aguilar-Lemarroy
José. F. Muñoz-Valle
Ana Laura Pereira-Suárez
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Cancer Cell International / Issue 1/2015
Electronic ISSN: 1475-2867
DOI: https://doi.org/10.1186/s12935-015-0234-9

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Abstract

Background

Methods

Results

Conclusion

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