Expression Levels of Key Components of the Hedgehog Pathway and an Investigation of the Correlation of this Pathway with Expression Levels of Claudin-۱ in Invasive Breast Carcinoma

Objective: Breast cancer is considered a heterogeneous disease, characterized by different biological and phenotypic features which make its diagnosis and treatment challenging. We have sought to investigate the expression levels of key components of the Hedgehog signaling pathway, correlation between the signal transducer Smo, and clinicopathologic features (lymph node metastasis and metastasis stage) in invasive breast carcinoma. Also, we examined the inverse correlation between expression levels of Smo and Claudin-۱ (an important gene involved in cell tight junctions). Methods: In this case-control study, we assessed ۳۶ pairs of tumor and adjacent normal tissue specimens obtained from patients with invasive ductal breast carcinoma. The expression levels of key components of Hedgehog signaling (Smo, Gli۱ and Ptch), Claudin-۱, E-cadherin, and MMP۲ were measured by qRT-PCR. The correlations between Smo expression with some clinicopathologic parameters were also analyzed. Results: We found up-regulation of Hedgehog signaling in invasive breast carcinoma samples compared to normal adjacent tissues.  Upregulation of the signal transducer Smo correlated with tumor stages and lymph node metastasis of the breast tumors. Interestingly, this correlation was affected by the expression of Her۲. A significant correlation existed between expression levels of the signal transducer Smo and Claudin-۱, E-cadherin as an epithelial cell marker, and MMP۲ as a metastasis-related gene in advanced metastatic tumor samples. Conclusion: Taken together, our study revealed a new layer of molecular complexity which should be considered in the management of patients with invasive breast carcinoma. The results suggested a key role for Hedgehog signaling in invasive breast carcinoma. In terms of the inverse correlation between expression levels of Claudin-۱ and Hedgehog signaling, Claudin-۱ could serve as a candidate gene in diagnostic studies. Thus, its clinical significance should be further clarified.

کلیدواژه ها:

Claudin-۱ ، Breast Cancer ، Hedgehog signaling pathway ، Claudin-۱ ، Prognosis ، سرطان پستان ، مسیر پیام رسانی Hedgehog ، پیش آگهی