Schwartz N, Chaudhri RA, Hadadi A, Schwartz Z, Boyan BD. 17Beta-estradiol promotes aggressive laryngeal cancer through membrane-associated estrogen receptor-alpha 36. Horm Cancer. 2014 Feb;5(1):22-32. PubMed PMID: 24081562.

Horm Cancer. 2014 Feb;5(1):22-32. doi: 10.1007/s12672-013-0161-y. Epub 2013 Oct 1.

17Beta-estradiol promotes aggressive laryngeal cancer through membrane-associated estrogen receptor-alpha 36.

Schwartz N(1), Chaudhri RA, Hadadi A, Schwartz Z, Boyan BD.

Author information:
(1)Department of Otolaryngology, Meir Hospital, Tchernichovsky 59, Kfar Saba, 44299, Israel.

17β-estradiol (E2) plays a key role in tumorigenesis by enhancing cell survivability and metastasis through its cytoplasmic receptors. Recently, a variant of estrogen receptor alpha, ERα36 has been implicated as a substantial mediator of E2's proliferative and antiapoptotic effects through rapid membrane-associated signaling, and cancers previously regarded as hormone-independent due to the absence of traditional receptors, may in fact be susceptible to E2. Despite rising from a secondary sex organ and having a clear gender disposition, laryngeal cancer is not uniformly accepted as hormone dependent, even in the face of compelling evidence of E2 responsiveness. The aim of this study was to further elucidate the role of E2 in the tumorigenesis of laryngeal cancer, both in vitro and in vivo. ERα36 presence was evaluated in membranes of the laryngeal carcinoma cell line, Hep2, as well as in laryngeal tumor samples. In vitro ERα36 was found to mediate rapid activation of protein kinase C and phospholipase D by E2, leading to increased proliferation and protection against chemotherapy-induced apoptosis. Furthermore, in response to E2 activation of ERα36, an upregulation of angiogenic and metastatic factors was observed. Clinical analysis of laryngeal tumors revealed a similar association between the amount of ERα36 and VEGF and indicated a role in lymph node metastasis. These findings present compelling evidence of ERα36-dependent E2 signaling in laryngeal cancer. Thus, targeting ERα36 may reduce the deleterious effects of E2 in laryngeal cancer, ultimately suggesting the importance of antiestrogen therapy or the production of novel drugs that specifically target ERα36.

PMCID: PMC3947116
PMID: 24081562  [PubMed - indexed for MEDLINE]

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