Abstract B62: Estrogen receptors interacting proteins and female lung cancer prognosis Free

The lung cancer death rate in women has doubled over the past 25 years, while the male lung cancer death rate has continued to decline. Although several lines of evidence suggest that women may be more susceptible to develop tobacco-induced lung cancer than men, we lack definitive results related to gender disparity in lung cancer survival. We hypothesize that estrogen through interaction with estrogen receptors (ERs) may mediate the centrosome amplification and affect their function. Potentially, centrosome abnormalities may lead to chromosomal instability and female lung cancer progression, that might be the reason for gender differences in lung cancer survival.

The NSCLC lung tumor specimens from male and female patients treated surgically at the Moffitt Cancer Center between 2000 and 2005 were used in this study.We developed quantitative methods for detection of centosome abnormalities and expression of γ- tubulin and Aurora A (markers of centrosome amplification) in archived tissue specimens and in lung cancer cell lines. We detected centosome markers and ER with immunocyto- histolabeling and assessed marker expression at sub-cellular locations, using bright field and confocal microscopy. Centrosomes are apical to the nucleus and appear to colocalize with ERα signal.

We have found promising novel data on interaction of ERα, MUC1 and γ- tubulin and Aurora A. We observed significant increases in expression of ERα and centrosome markers in a subgroups of malignant tumors compared to normal adjacent lung. Co-localization experiments on cell culture encourage us to consider centrosome modification as the downstream effect of estrogen modification in lung cancer.

Correlation analysis of clinical data on differential lung cancer survival (after adjustment for patient’s gender, age, race, histology type, tumor stage at diagnosis, follow-up for recurrence and smoking history) with criteria of centrosome abnormalities is underway. These data may open a new way to look on mechanisms of chromosomal instability under estrogen control in female lung cancer progression, and introduce an attractive, novel therapeutic target.

Citation Information: Cancer Prev Res 2008;1(7 Suppl):B62.