A role of calcitonin receptor family on progression of breast cancer

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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