A role of calcitonin receptor family on progression of breast cancer

越来越多的证据表明降钙素（CT）及其受体（CTR）参与细胞生长、分化和组织发育。利用激光捕获显微解剖（LCM）和实时逆转录聚合酶链反应（RT-PCR），我们研究了60例原发性乳腺癌中CTR mRNA的表达，包括来自同一患者的14对匹配癌和未受影响的导管上皮。我们的研究结果表明，CTR mRNA在正常导管上皮和乳腺癌中持续表达。在可获得匹配样本的14例中，9例乳腺癌（64.3%）的CTR mRNA表达降低，2例（14.3%）的CTR mRNA表达升高，3例（21.4%）的CTR mRNA表达无显著变化。60例原发性乳腺癌中，CTR表达降低44例（73.3%），CTR表达升高10例（16.7%），无变化6例（10%）。CTR表达降低在淋巴结转移（p=0.0498）和淋巴浸润（p=0.0179）中更为常见。此外，在广泛导管内成分（p=0.0543）和高核分级（p=0.1934）的病例中，CTR表达降低，尽管这没有统计学意义。总的来说，我们得出结论，CTR mRNA在未受影响的导管上皮中持续表达，而CTR mRNA表达减少在乳腺癌中经常发现，特别是在淋巴结转移和淋巴浸润的情况下。MDA-MB-231人乳腺癌细胞，代表转移，ERK1/2组成性磷酸化。CT通过PKA途径灭活c-Raf，抑制Erk1/2磷酸化，最终降低MDA-MB-231细胞中uPA的表达。CT对MDA-MB-231细胞的侵袭率降低（P<0.05）。这些数据表明，乳腺癌转移至少部分归因于活化的ERK通路，CT抑制活化的ERK1/2并抑制MDA-MB-231乳腺癌细胞的侵袭性。CTR在乳腺癌进展中可能具有重要的潜在意义。少

There is a growing body of evidence indicating that Calcitonin(CT) and its receptor(CTR) is involved in cell growth, differentiation and tissue development. Using laser capture microdissection(LCM) and real-time reverse transcription polymerase chain reactions(RT-PCR), we have investigated CTR mRNA expression in 60 primary breast cancers, including 14 pairs of matched cancers and unaffected ductal epithelia from the same patients. Our results demonstrate that CTR mRNA was constantly expressed in normal ductal epithelium and in breast cancer. In the 14 cases where matched samples were available, a decrease in CTR mRNA expression was found in 9 breast cancers (64.3%), an increased CTR expression in 2 cases (14.3%) and no significant change in 3 cases (21.4%). In 60 cases of primary breast cancers, decreased CTR expression was found in 44 (73.3%), increased CTR expression was detected in 10 cases (16.7%) and no change was observed in 6 cases (10%). Decreased CTR expression was found more … More often in cases with lymph node metastasis (p=0.0498) and lymphatic invasion (p=0.0179). Also there was a decreased CTR expression in cases with an extensive intraductal component (p=0.0543) and a high nuclear grade (p=0.1934), although this was not statistically significant. Overall, we conclude that CTR mRNA was constantly expressed in unaffected ductal epithelium, whereas decreased CTR mRNA expression was frequently found in breast cancers, particularly in cases with lymph node metastasis and lymphatic invasion.MDA-MB-231 human breast cancer cells, which represent metastatic, ERK1/2 phosphorylated constitutively., CT inactivates c-Raf via the PKA pathway, resulting in suppression of Erk1/2 phosphorylation, and finally decreases uPA expression in MDA-MB-231 cells. CT caused a decrease in invasion of MDA-MB-231 cells in Matrigel invasion assays (P<0.05). These data suggested that breast cancer metastasis was at least partially attributable to activated ERK pathway, and CT suppresses activated ERK1/2 and inhibits invasiveness in MDA-MB-231 breast cancer cells. CTR might be of great potential significance in breast cancer progression. Less