Estrogen receptor beta and CXCR4/CXCL12 expression: differences by sex and hormonal status in lung adenocarcinoma.
OBJECTIVE
Studies have reported differences in lung cancer behavior between sex and hormonal status that suggest a role of estrogens and estrogen receptor beta (ERβ) in lung carcinogenesis. In some types of hormone-dependent cancer, estrogens may regulate CXCL12/CXCR4 expression through ERβ signaling. High expression of CXCL12/CXCR4 is associated with poor prognosis in lung cancer because it promotes tumor growth and metastasis. Therefore, in this study we investigated whether lung adenocarcinoma tissues from pre- and postmenopausal women and from men exhibit different ERβ, CXCR4/CXCL12 expression and whether this expression is associated with clinicopathological features.


METHODS
Sixty primary tumor samples of lung adenocarcinoma from pre- and postmenopausal women and from men were collected for this study. Thirty samples of healthy lung tissue adjacent to the tumor site were used as controls. ERβ and CXCL12/CXCR4 expression was analyzed by immunohistochemistry. Expression of these proteins was measured by digital image software and compared between sex and hormonal status.


RESULTS
Lung adenocarcinomas overexpressed ERβ, CXCR4 and CXCL12 compared to normal lung. Moreover, lung adenocarcinomas from premenopausal women exhibited higher signals for ERβ, CXCL12 and CXCR4 compared to postmenopausal women and to men, who showed lower signals for these proteins. A multivariate analysis revealed a strong association between the immunoreactivity level of ERβ, CXCL12/CXCR4 and both sex and hormonal status, but not with tumor stage and smoking.


CONCLUSIONS
These results demonstrated that ERβ and CXCL12/CXCR4 expression in lung adenocarcinoma depends on sex and hormonal status, which may partly explain the sex and hormonal differences in lung cancer behavior.
Departamento de Biología Celular y Tisular, Facultad de Medicina, UNAM, México, D.F., Mexico. Electronic address: vianeyrodriguezlara@yahoo.com.mx.
Vianey
V
Rodriguez-Lara
Instituto Nacional de Enfermedades Respiratorias "Ismael Cosio Villegas", México, D.F., Mexico.
Erika
E
Peña-Mirabal
Instituto Nacional de Enfermedades Respiratorias "Ismael Cosio Villegas", México, D.F., Mexico.
Renata
R
Baez-Saldaña
Departamento de Inmulogía, Instituto de Investigaciones Biomédicas, UNAM, México, D.F., México.
Ana Luisa
AL
Esparza-Silva
Departamento de Inmulogía, Instituto de Investigaciones Biomédicas, UNAM, México, D.F., México.
Eduardo
E
García-Zepeda
Facultad de Quimica, UNAM, Mexico.
Marco Antonio
MA
Cerbon Cervantes
Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, UNAM, México, D.F., México.
Daniel
D
Diaz
Departamento de Biología Celular y Tisular, Facultad de Medicina, UNAM, México, D.F., Mexico.
Teresa Imelda
TI
Fortoul
D000230:Adenocarcinoma / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054377:Chemokine CXCL12 / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017698:Postmenopause; D017697:Premenopause; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012737:Sex Factors; D015398:Signal Transduction
D054377:Chemokine CXCL12; D047629:Estrogen Receptor beta; D004967:Estrogens; D019718:Receptors, CXCR4
CXCL12/CXCR4; ERβ; Lung cancer; estrogen; premenopausal women