The parathyroid hormone-related protein receptor is expressed in breast cancer bone metastases and promotes autocrine proliferation in breast carcinoma cells.
The parathyroid hormone-related protein receptor is expressed in breast cancer bone metastases and promotes autocrine proliferation in breast carcinoma cells.
复制标题
DOI：
10.1038/sj.bjc.6600757
复制
发表时间：
2003-02-24
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
甲状旁腺相关蛋白（PTHRP）的过度产生发生在高比例的原发性乳腺癌（PBC）中，并与其向骨的转移扩散密切相关。虽然PTHRP受体（PTHRP-R）通常与PTHRP在PBC中共表达，但其在调节乳腺癌细胞增殖和骨转移中的作用仍不清楚。本研究的目的是确定PTHRP-R在乳腺癌骨转移（BM）中的表达，并研究PTHRP-R过表达对乳腺癌细胞增殖的影响。PTHRP-R在BM中的表达率为85%（11/13），而在PBC中的表达率为58%（39/67）。BM的中位表达高于PBC（P<0.05）。PTHRP增加稳定过表达PTHRP-R的MCF-7细胞（MCF-7 WTR）的cAMP积累和DNA合成，但在MCF-7VEC对照细胞中不增加。DNA合成的增加由cAMP途径激活剂毛喉素模拟。受体拮抗剂PTHRP 7 -34减少MCF-7 WTR细胞中的DNA合成，但不减少MCF-7VEC细胞中的DNA合成，表明受体过表达促进PTHRP 7 - 34的自分泌活性。MCF-7 WTR细胞对胎牛血清的促有丝分裂反应性增加，倍增时间减少。PTHRP诱导ERK 1和ERK 2的弱激活，并通过血清生长因子增强其激活。总的来说，这些结果表明PTHRP-R经常在乳腺癌BM中表达，并表明受体过表达通过cAMP和ERK途径介导的自分泌信号驱动增殖。
Overproduction of parathyroid hormone-related protein (PTHRP) occurs in a high proportion of primary breast cancers (PBC) and is strongly implicated in their metastatic spread to bone. Although the PTHRP-receptor (PTHRP-R) is often coexpressed with PTHRP in PBC, its role in regulating breast cancer cell proliferation and metastases to bone remains unclear. The aims of this study were to determine the expression of the PTHRP-R in breast cancer bone metastases (BM) and to investigate the effects of PTHRP-R overexpression on breast cancer cell proliferation. PTHRP-R expression occurred in 85% (11 out of 13) of BM compared with 58% (39 out of 67) of PBC. Median expression was higher (P<0.05) in BM compared with PBC. PTHRP increased cAMP accumulation and DNA synthesis in MCF-7 cells stably overexpressing the PTHRP-R (MCF-7WTR) but not in MCF-7VEC control cells. The increase in DNA synthesis was mimicked by the cAMP pathway activator forskolin. The receptor antagonist PTHRP7–34 reduced DNA synthesis in MCF-7WTR cells, but not MCF-7VEC cells, indicating that receptor overexpression promotes autocrine PTHRP activity. MCF-7WTR cells showed increased mitogenic responsiveness to fetal calf serum and reduced doubling times. PTHRP induced weak activation of ERK1 and ERK2 and potentiated their activation by serum growth factors. Collectively these results show that the PTHRP-R is frequently expressed in breast cancer BM and indicate that receptor overexpression drives proliferation via autocrine signals that are mediated via cAMP and ERK pathways.
登录
查看更多内容
影响因子：
8.8
作者：
Birch MA;Carron JA;Scott M;Fraser WD;Gallagher JA
通讯作者：
Gallagher JA
DOI：
10.1016/0006-291x(89)92826-x
发表时间：
1989-02-15
影响因子：
3.1
作者：
NAGASAKI, K;YAMAGUCHI, K;ABE, K
通讯作者：
ABE, K
DOI：
10.1006/bbrc.1999.1659
发表时间：
1999-11-11
影响因子：
3.1
作者：
Rong, HQ;Ji, H;Bucht, E
通讯作者：
Bucht, E
影响因子：
8.8
作者：
Carron JA;Fraser WD;Gallagher JA
通讯作者：
Gallagher JA
DOI：
10.1073/pnas.95.5.2648
发表时间：
1998-03-03
影响因子：
11.1
作者：
Chen, JH;Bander, JA;Iyengar, R
通讯作者：
Iyengar, R