産婦人科における細胞増殖因子の意義

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In this lecture, importance of growth factors in reproductive functions and cancer growth are discussed. Among many kinds of growth factors, epidermal growth factor (EGF) and transforming growth factor (TGF)α are mentioned ; both of these are called as EGF family because these share a common receptor (EGF receptor) and show similar biological activities. It is known that growth factors are important in reproductive fields. They play vital roles in the follicle development and the endometrial proliferation ill response to estrogen. We studied the expression and role of EGF and TGFα in human fallopian tube. Immunohistochemical and RT-PCR studies revealed the menstrual stages specific synthesis and expression of EGF and TGFα in tubal epithelial cells. They were abundant at the late follicular and luteal stages, were little at the early follicular stage, suggesting that these growth factors are expressed in response to estrogen. We, next, examined the role of these factors in early embryo development using mouse embryos. Embryo development was significantly improved when embryos were co-cultured with human tubal epithelial cells. However, the favorable effects of the tubal epithelial cells were almost completely abolished by the addition of anti-EGF and -TGFα neutralizing antibodies. These facts suggest that EGF and EGFα expressed in human epithelial cells promote embryo development in a paracrine manner. Autocrine mechanisms by growth factors are known to be important on cancer cell growth. Among many kinds of autocrine mechanisms TGFα/EGF receptor autocrine mechanism is the most commonly expressed in many kinds of cancers such as lung cancer, esophageal cancer, pancreas cancer and liver cancer. We studied the expression and the biological role of TGFα/EGF receptor autocrine mechanism in human ovarian cancers. As many as 57% of primary human ovarian cancers expressed EGF receptors by ^<125>I-EGF binding studies in 35 cases of ovarian cancers, and these EGF receptor expressing ovarian cancers also expressed TGFα, but not EGF. TGFα significantly enhanced the growth of ovarian cancer cells, and, moreover, anti-TGFα or anti-EGF receptor antibodies significantly inhibited the ovarian cancer cell growth in vitro and in vivo. All these results indicate that TGFα/EGF receptor autocrine mechanism is commonly expressed in human ovarian cancers, and plays an important role on their growth. It was noteworthy that similar autocrine mechanisms by growth factors are expressed and play important roles in both reproductive systems and in cancer cells. Considering the fact that many kinds of growth factors also play important roles on feto-placental development, it might be reasonable to mention that "growth factors" are important in all gynecological and obstetrical fields.
社団法人日本産科婦人科学会の論文
1994-08-01

産婦人科における細胞増殖因子の意義

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