Overexpression of AKT2/protein kinase Bbeta leads to up-regulation of beta1 integrins, increased invasion, and metastasis of human breast and ovarian cancer cells.
Overexpression of AKT2/protein kinase Bbeta leads to up-regulation of beta1 integrins, increased invasion, and metastasis of human breast and ovarian cancer cells.
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发表时间：
2003
期刊：
影响因子：
11.2
通讯作者：
M. Arboleda;J. Lyons;F. Kabbinavar;M. Bray;B. Snow;Raul Ayala;Mordechai Danino;B. Karlan;D. Sla
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文献类型：
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作者：
M. Arboleda;J. Lyons;F. Kabbinavar;M. Bray;B. Snow;Raul Ayala;Mordechai Danino;B. Karlan;D. Sla
为了确定AKT 2如何促进肿瘤细胞进展，将全长野生型人AKT 2/蛋白激酶B（PKB）β cDNA转染到一组8个人乳腺癌和卵巢癌细胞中。由于β 1整合素的上调，AKT 2转染子表现出通过IV型胶原的粘附和侵袭增加。此外，AKT 2细胞在体内比对照细胞更具转移性。通过与抗β 1整合素功能阻断抗体预孵育、暴露于渥曼青霉素以及通过表达磷酸酶和张力蛋白同源物肿瘤抑制因子（PTEN）来阻断AKT 2增加的侵袭。对转染的人乳腺癌细胞进行的共聚焦显微镜检查显示，与AKT 1不同，AKT 2蛋白在细胞附着期间主要位于IV型胶原基质附近。过表达AKT 2，而不是AKT 1或AKT 3，足以复制乳腺癌细胞中转染的磷酸肌醇3-OH激酶（PI 3-K）的侵袭作用。此外，激酶死亡AKT 2（181个氨基酸甲硫氨酸[M]）的表达，而不是激酶死亡AKT 1（179 M）或AKT 3（177 M）的表达，能够阻断由人表皮生长因子受体-2（HER-2）过表达或PI 3-K激活诱导的侵袭。总之，这些数据表明，AKT 2介导的PI 3-K依赖性的影响粘附，运动，侵袭和转移体内。
To determine how AKT2 might contribute to tumor cell progression, a full-length, wild-type, human AKT2/protein kinase B (PKB)beta cDNA was transfected into a panel of eight human breast and ovarian cancer cells. AKT2 transfectants demonstrated increased adhesion and invasion through collagen IV because of up-regulation of beta1 integrins. In addition, AKT2 cells were more metastatic than control cells in vivo. Increased invasion by AKT2 was blocked by preincubation with an anti-beta1 integrin function blocking antibody, exposure to wortmannin, and by expression of phosphatase and tensin homologue tumor suppressor (PTEN). Confocal microscopy performed on transfected human breast cancer cells showed that unlike AKT1, AKT2 protein predominantly localized adjacent to the collagen IV matrix during cellular attachment. Overexpression of AKT2, but not AKT1 or AKT3, was sufficient to duplicate the invasive effects of phosphoinositide 3-OH kinase (PI3-K) transfected in breast cancer cells. Furthermore, expression of kinase dead AKT2(181 amino acid methionine [M]), and not kinase dead AKT1(179M) or AKT3(177M), was capable of blocking invasion induced by either human epidermal growth factor receptor-2 (HER-2) overexpression or by activation of PI3-K. Taken together, these data indicate that AKT2 mediates PI3-K-dependent effects on adhesion, motility, invasion, and metastasis in vivo.