Defense Date

7-16-2003

Graduation Date

Summer 2003

Availability

Immediate Access

Submission Type

thesis

Degree Name

MS

Department

Biological Sciences

Committee Chair

Kyle W. Selcer

Committee Member

John S. Doctor

Committee Member

Richard P. Elinson

Keywords

breast cancer, MCF-7, MDA-MB-231, steroid sulfatase, steroid sulfatase immunoreactivity

Abstract

Breast cancer is the most frequently occurring cancer in women and is the second leading cause of death. About 40% of breast cancers are hormone-dependent and require estrogen for their growth. The steroid sulfatase pathway is an important means of converting local inactive estrogens to their active forms, thus supporting tumor growth. A substantial amount of research has been performed in the design of steroid sulfatase inhibitors, but the regulation of steroid sulfatase has been largely overlooked. My goal was to study the regulation of steroid sulfatase by different steroid hormones, using two human breast cancer cell lines the hormone-dependent MCF-7, and the hormone-independent MDA-MB-231. I also studied the effect of various growth factors (oxytocin, prolactin, IGF-1 and EGF) on steroid sulfatase activity of MDA-MB-231 cells. MDA-MB-231 cells treated in whole growth medium showed a decrease in steroid sulfatase activity, whereas, those treated with cortisol had a decrease in steroid sulfatase activity. Estradiol and estrone sulfate had no effect on steroid sulfatase activity in MDA-MB-231 cells. No differences in steroid sulfatase activity were found for any treatments in hormone-dependent MCF-7 cells. Growth factors also did not have any effect on the steroid sulfatase activity in MDA-MB-231 cells. Recent evidence shows that steroid sulfatase immunoreactivity is associated with breast cancer relapse. Hence, steroid sulfatase could be an independent predictive marker for breast cancer. My other aim was to evaluate different human tissues for steroid sulfatase status by immunohistochemistry. The results showed that placenta, liver, normal breast, breast carcinoma (ER+/ PR+) and skeletal muscle had high immunoreactivity for steroid sulfatase. Skin, lung, brain and uterine carcinoma showed moderate steroid sulfatase activity, whereas, adrenal gland, breast carcinoma (ER-/ PR-), ovarian carcinoma and prostate had very low steroid sulfatase activity. The study of regulation and inhibition of steroid sulfatase may be important in treatment, prognosis and reduction of mortality due to breast cancer.

Format

PDF

Language

English

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