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。采用激光捕获显微切割（LCM）和实时逆转录聚合酶链反应（RT-PCR），我们研究了CTR mRNA的表达在60原发性乳腺癌，包括14对匹配的癌症和未受影响的导管上皮从同一患者。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。14例乳腺癌组织中，CTR mRNA表达降低9例（64.3%），表达升高2例（14.3%），无明显变化3例（21.4%）。60例乳腺癌组织中，CTR表达降低44例（73.3%），表达升高10例（16.7%），无变化6例（10%）。CTR表达降低者， 关于我们 多见于淋巴结转移（p = 0.0498）和淋巴管浸润（p = 0.0179）。此外，在具有广泛导管内成分（p = 0.0543）和高核分级（p = 0.1934）的病例中，CTR表达降低，尽管这在统计学上不显著。总之，我们得出结论，CTR mRNA在未受影响的导管上皮中持续表达，而在乳腺癌中经常发现CTR mRNA表达降低，特别是在淋巴结转移和淋巴浸润的情况下。CT通过PKA途径使c-Raf失活，导致Erk 1/2磷酸化的抑制，并最终降低MDA-MB-231细胞中uPA的表达。Matrigel侵袭实验显示CT可降低MDA-MB-231细胞的侵袭能力（P <0.05）。这些数据表明，乳腺癌转移至少部分归因于激活的ERK通路，并且CT抑制激活的ERK 1/2并抑制MDA-MB-231乳腺癌细胞的侵袭性。CTR可能在乳腺癌的进展中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