BMP-2 upregulates the AKT/mTOR pathway in breast cancer with microcalcification and indicates a poor prognosis.

Abstract

BACKGROUND:

As a reliable biomarker of breast cancer, breast microcalcification has been reported to be correlated with poor prognosis. Bone morphogenetic protein 2 (BMP-2) plays an important role in microcalcification of breast cancer. Studies in other tissues have shown an association between BMP-2 and AKT/mTOR pathway, while their relationship in breast cancer still remains largely undetermined. To clarify the relationship of these three factors, we collected patients of invasive breast cancer with/without microcalcification and immunohistochemical examination was performed.

METHOD/PATIENTS:

A total of 272 patients with primary invasive breast cancer were selected from the First Hospital of China Medical University from January 2010 to January 2012. Immunohistochemical examination of the BMP-2, p-AKT and p-mTOR was performed on 4-µm tissue microarray (TMA) sections. Then, we analyzed the relationship of BMP-2, p-AKT, and p-mTOR and their correlation with disease-free survival (DFS) in breast cancer with/without microcalcification.

RESULTS:

We found that breast cancer patients with microcalcification were correlated with HER-2 positive expression and poor prognosis. Immunohistochemical examination showed that the expressions of BMP-2 and p-mTOR were increased in breast cancer with microcalcification and the expressions of BMP-2, p-AKT, and p-mTOR were correlated with each other. Moreover, the high expressions of BMP-2, p-AKT, and p-mTOR were significantly correlated with poor prognosis.

CONCLUSIONS:

Based on the abovementioned findings, we hypothesized that the high expression of BMP-2 not only played a vital role in the formation of microcalcification, but also activated the AKT/mTOR pathway. Collectively, breast cancer patients with microcalcification were more likely to be resistant to targeted or endocrine therapy and be correlated with poor prognosis.

• Authors: S Wang, M Gu, H Jiang, X Zheng
• Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico (Clin Transl Oncol) Vol. 22 Issue 8 Pg. 1263-1271 (Aug 2020) ISSN: 1699-3055 [Electronic] Italy
• PMID: 31863351 (Publication Type: Journal Article)

Chemical References

• BMP2 protein, human
• Bone Morphogenetic Protein 2
• Neoplasm Proteins
• MTOR protein, human
• ERBB2 protein, human
• Receptor, ErbB-2
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Adult
• Bone Morphogenetic Protein 2 (metabolism)
• Breast Neoplasms (metabolism, mortality, pathology)
• Calcinosis (etiology, metabolism, mortality)
• Female
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Middle Aged
• Neoplasm Proteins (metabolism)
• Prognosis
• Proto-Oncogene Proteins c-akt (metabolism)
• Receptor, ErbB-2 (metabolism)
• Regression Analysis
• TOR Serine-Threonine Kinases (metabolism)
• Tissue Array Analysis
• Up-Regulation