MMP7 expression regulated by endocrine therapy in ERβ-positive colon cancer cells

Apoptosis was evaluated using flow cytometry. The expression of matrix metalloproteinases 7 (MMP-7) and estrogen receptor beta (ERβ) was measured by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. The migration capability of treated cells was determined with wound scratch assay.Tamoxifen alone, 5-FU alone, and the combination of the two drugs can significantly inhibit HT29 cell proliferation and migration, block the cells in G2/M phase and induce cell apoptosis. These drugs also can down-regulate MMP7 and ERβ expression.Our findings suggest that endocrine therapy is an efficient therapy for inhibiting ERβ-positive colon cancer cell proliferation and migration via down-regulation of MMP7.Colorectal cancer is a growing health problem. In 2002 over one million new cases of colorectal cancer were diagnosed, and 529,000 people died from the disease, with the majority of deaths attributable to distant metastases [1]. The liver is a frequent site of colorectal metastases, and 15% to 25% of these patients have liver metastases at diagnosis [2]. About 50% to 60% of colorectal cancer patients will eventually develop advanced or metastatic disease [3]. Despite advances in survival with chemotherapy or surgical resection of hepatic metastases, the majority of patients still experience disease recurrence [4].Many studies observed that the estrogen receptor beta (ERβ) is significantly related to cancer metastases [5-7]. Kuiper et al. first characterized ERβ in the rat prostate and ovary [8]. ERβ is the dominant receptor in human colonic mucosa, as many studies have shown that ERβ is more highly expressed than ERα in colon tissue [9-12]. Animal studies also revealed roles for ERβ in many tissues and organs, including the ovary, uterus, mammary gland, ventral prostate, salivary gland, immune system and central nervous system [13-17]. Currently, ERβ is the only ER identified in colon cell lines [10].ERα and ERβ belong to a super-family of nuclear hormone r