Han Bo, Nakamura Misa, Zhou Gengyin, Ishii Aiko, Nakamura Atsushi, Bai Yanhua, Mori Ichiro, Kakudo Kennichi
Department of Pathology, Wakayama Medical University, Wakayama 641-8509, Japan.
Int J Oncol. 2006 Apr;28(4):807-14.
There is a growing body of evidence indicating that calcitonin (CT) and calcitonin receptor (CTR) are involved in the regulation of cell growth, differentiation, and survival and in tissue development. However, the precise functional role of CT/CTR in breast cancer is still unknown. It is well established that the urokinase plasminogen activator (uPA) system plays an important role in breast cancer invasion and metastasis. The goal of this study was to investigate the effects of CT on regulation of the uPA system and invasive capacity of breast cancer cells. In the highly invasive MDA-MB-231 cell line, 10(-8) M CT decreased both uPA and uPAR mRNA and protein expression which was associated with inhibition of the extracellular signal-regulated kinase (ERK) 1/2 pathway. Furthermore, two weeks of CT administration to nude mice inhibited the expression of uPA mRNA in primary tumors by 25% (P<0.05), as compared to control, untreated animals. CT also inhibited the invasiveness of MDA-MB-231 cells by 37% (10(-8) M CT, P<0.05), as determined by a Matrigel invasion assay. To the best of our knowledge, this is the first report describing a direct effect of CT on breast cancer cell invasion. Our data might suggest a close link between CT signaling, the uPA-mediated pathway, and breast cancer invasion.
越来越多的证据表明，降钙素（CT）和降钙素受体（CTR）参与细胞生长、分化和存活的调节以及组织发育。然而，CT/CTR在乳腺癌中的确切功能作用仍不清楚。尿激酶型纤溶酶原激活剂（uPA）系统在乳腺癌侵袭和转移中起重要作用，这一点已得到充分证实。本研究的目的是探讨CT对uPA系统调节及乳腺癌细胞侵袭能力的影响。在高侵袭性的MDA-MB-231细胞系中，10(-8) M的CT降低了uPA和uPAR的mRNA及蛋白表达，这与细胞外信号调节激酶（ERK）1/2通路的抑制有关。此外，与未处理的对照裸鼠相比，给裸鼠连续两周注射CT可使原发肿瘤中uPA mRNA的表达降低25%（P<0.05）。通过基质胶侵袭试验测定，CT还使MDA-MB-231细胞的侵袭能力降低了37%（10(-8) M CT，P<0.05）。据我们所知，这是第一份描述CT对乳腺癌细胞侵袭有直接作用的报告。我们的数据可能提示CT信号传导、uPA介导的通路与乳腺癌侵袭之间存在密切联系。
