Cohen P, Lamson G, Okajima T, Rosenfeld R G
Department of Pediatrics, Stanford University Medical Center, CA 94305.
Growth Regul. 1993 Mar;3(1):23-6.
The insulin-like growth factors (IGFs) are potent mitogens with both endocrine and autocrine-paracrine effects on cell growth. The insulin-like growth factor binding proteins (IGFBPs) are found in many human biological fluids and in the conditioned media of many cell cultures. These molecules are ontogenically and hormonally regulated. Nevertheless, the biological role(s) of the IGFBPs remain controversial. Both inhibitory and stimulatory effects of IGFBPs on cell growth have been suggested. In order to evaluate the actions of endogenously produced IGFBPs on cell growth, we have constructed a mammalian expression vector containing the hIGFBP-3 cDNA, and transfected the murine Balb/c cell line. The IGFBP-3 transfected Balb/c cells (Tx-BP-3) expressed readily detectable amounts of hIGFBP-3 protein and its mRNA. Growth of Tx-BP-3 in serum containing media was significantly slower, compared with control plasmid-transfected cells (Tx-P) grown under identical conditions. Fully confluent Tx-BP-3 cells arrested their growth at a cell density that was lower than did Tx-P cells. When transfected cells were grown in insulin-containing media, growth rates of the IGFBP-3 transfected cells were not restored to those observed in control plasmid-transfected cells. These results suggest that in this model, the expression of endogenous IGFBP-3 has an inhibitory effect on cell growth.
胰岛素样生长因子（IGFs）是强大的促有丝分裂原，对细胞生长具有内分泌和自分泌-旁分泌作用。胰岛素样生长因子结合蛋白（IGFBPs）存在于许多人体生物体液以及许多细胞培养物的条件培养基中。这些分子在个体发育和激素水平上受到调控。然而，IGFBPs的生物学作用仍存在争议。有人提出IGFBPs对细胞生长既有抑制作用也有刺激作用。为了评估内源性产生的IGFBPs对细胞生长的作用，我们构建了一个包含hIGFBP - 3 cDNA的哺乳动物表达载体，并转染了小鼠Balb/c细胞系。转染了IGFBP - 3的Balb/c细胞（Tx - BP - 3）能够表达易于检测到的hIGFBP - 3蛋白及其mRNA。与在相同条件下生长的对照质粒转染细胞（Tx - P）相比，Tx - BP - 3在含血清培养基中的生长明显较慢。完全汇合的Tx - BP - 3细胞在低于Tx - P细胞的细胞密度时就停止了生长。当转染细胞在含胰岛素的培养基中生长时，IGFBP - 3转染细胞的生长速率并未恢复到对照质粒转染细胞所观察到的水平。这些结果表明，在这个模型中，内源性IGFBP - 3的表达对细胞生长具有抑制作用。
