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Estrogen may be linked to spread of premalignant cells in head, neck
Shatalova EG. Cancer Prev Res. 2011;4:107-115.
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Researchers at Fox Chase Cancer Center have shown that a panel of estrogen metabolism genes is expressed in early- and late-stage head and neck lesions.
“Detection of transcripts for these genes in both premalignant lesions and [squamous cell carcinoma of the head and neck] suggests that these enzymes contribute to cellular metabolism throughout tumorigenesis,” the researchers wrote.
The study aimed to determine how estrogens contribute to the development of squamous cell carcinoma of the head and neck (SCCHN), the sixth most common type of cancer in the US. Researchers obtained a range of cell lines from early- and late-state lesions to characterize the expression of estrogen synthesis and metabolism genes, study the effect of estrogen on gene expression and assess the role of CYP1B1 and/or estrogen in cell motility, proliferation and apoptosis.
According to the results, CYP1B1, CYP1A1, COMT, UGT1A1 and GSTP1, along with estrogen receptor-beta, were expressed in cell lines originating from both premalignant (MSK-Leuk1) and malignant SCCHN lesions. In premalignant cells, estrogen exposure was associated with a 2.3- to 3.6-fold increase in CYP1B1 induction compared with vehicle-treated controls (P=.0004). This association was not observed in SCCHN cells.
Cell migration was reduced by 57% and proliferation by 45% after CYP1B1 knockdown by short-hairpin RNA. In addition, exposure to estrogen was associated with a 26% decrease in apoptosis among premalignant cells, but supplementation with fulvestrant (Faslodex, AstraZeneca) led to the restoration of estrogen-dependent apoptosis.
The researchers used tissue microarrays to examine head and neck tissues of 128 patients for estrogen pathway representation. Immunohistochemical staining occurred for estrogen receptor-beta (91.9% of samples), CYP1B1 (99.4% of samples) and 17-beta-estradiol (88.4% of samples). Compared with normal epithelium, SCCHNs exhibited elevated CYP1B1 (P=.024) and estrogen receptor-beta (P=.008).
“These data provide novel insight into the mechanisms underlying head and neck carcinogenesis and facilitate the identification of new targets for chemopreventive intervention,” the researchers wrote.
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