유방암 세포에서 Retinoic acid에 의한 Insulin-like growth factors와 Insulin-like growth factor binding protein-3 분비 조절에 있어서 PKC와 cAMP의 역할 = (The) regulatory mechanism of Insulin-like growth factors and Insulin-like growth factor binding protein-3 secretion by Retinoic acid in breast cancer cell (MCF-7) : Involvement of PKC and cAMP

다국어 초록 (Multilingual Abstract)

Breast cancer has been known to be the most commonly diagnosed cancer in women. Retinoid acid(RA) induces growth inhibition and apoptosis in a variety of tumer cells, including breast cancer cells. IGFs system has been reported to be associated with the development of cancer. Although breast cancer cell with RA is to be the major stimulus for the cell growth, the mechanism of IGF system remains to be elucidated. Thus, this study was conducted to examine the effect of RA on the gene and protein expression of IGFs and IGFBP-3 also involvement of cAMP and PKC in breast cancer cells.
In this study, IGFs secretion was measured by radioimmunoassay (RIA), IGFBP-3 secretion by western ligand blotting(WLB) and IGFs and IGFBP-3 gene expression by RT-PCR. The results are as follows :
1) RA(≥ 10^(-6) M) decreased IGFs secretion and the gene expression of IGFs but increased IGFBP-3 secretion and gene expression.
2) IGFBP-3 antibody itself, but not immunogloblin G(Ig G) significantly increased IGFs secretion and mRNA levels. Pretreatment of IGFBP-3 antibody blocked RA-induced inhibition of IGFs secretion and mRNA levels. Moreover, IGFBP-3 antibody itself decreased IGFBP-3 secretion and mRNA levels and pretreatment of IGFBP-3 blocked RA-induced increase of IGFBP-3 secretion and mRNA expression.
3) 8-Br-cAMP(cAMP analogue) mimicked RA-induced inhibition of IGFs secretion and mRNA expression. Cotreatment of 8-Br-cAMP with RA has more potentiated inhibitory effect on IGFs than itself. SQ22536 blocked RA-induced inhibition of IGFs secretion and mRNA expression. 8-Br-cAMP also increased IGFBP-3 secretion and mRNA levels, mimicking atRA action. SQ22536 blocked RA-induced increase of IGFBP-3 secretion and mRNA levels.
4) PMA, a PKC activator, itself increased IGFs secretion and mRNA levels, but the cotreatment of PMA and RA increased the RA-induced inhibition of IGFs secretion and mRNA levels. Staurosporine(PKC inhibitor) itself decreased IGFs secretion and mRNA levels and potentiated RA-induced inhibition of IGFs secretion and mRNA levels. However, unlike IGFs secretion, PMA increased IGFBP-3 secretion and mRNA levels. Staurosporine itself decreased IGFBP-3 secretion and mRNA levels and blocked RA-induced increase of IGFBP-3 secretion and mRNA levels.
Therefore, RA inhibited IGFs secretion and mRNA levels via IGFBP-3 secretion. Furthermore, RA increased IGFBP-3 secretion and mRNA expression via cAMP. However, the involvement of PKC in RA-induced effect was limited to IGFBP-3 secretion and mRNA levels, but not IGFs secretion and mRNA levels.

목차 (Table of Contents)

• 목차 = ⅰ
• Abstract = 1
• 서론 = 5
• 재료 및 방법 = 8
• 결과 = 17
• 고찰 = 22
• 결론 = 29
• 참고문헌 = 31
• 부록 = 41