Breast Cancer Invasion and Metastasis by mPRα Through the PI3K/Akt Signaling Pathway

Pathol Oncol Res. 2016 Jul;22(3):471-6. doi: 10.1007/s12253-015-0023-8. Epub 2015 Nov 25.

Abstract

Invasive breast cancer is the most common type of malignancy in women worldwide. However, the mechanism responsible for breast cancer metastasis is still unclear and needs further illustration. It has been proven that matrix metallopeptidase 9 (MMP-9) promotes metastasis of the cancer cells. However, the interaction between mPRα and MMP-9 has not been studied. Therefore, in the present research, the effect of MMP-9 on the malignant progression of invasive breast cancer promoted by membrane progesterone receptorα (mPRα) was investigated. The results showed that the protein expression of mPRα, p-Akt and MMP-9 increased in the cancerous tissues compared to that of the noncancerous breast tissue. Furthermore, a positive correlation was found between mPRα and C-erbB-2, as well as the number of involved local lymph nodes. On the other hand, a negative correlation was observed between mPRα and estrogen receptors (ER) along with progesterone receptors (PR). Similarly, a positive association was found between MMP-9 and the number of involved local lymph nodes. Besides, the high expression of MMP-9 also had a positive correlation with the tumor size. However, the high level of MMP-9 had a negative correlation with ER and PR. In addition, there was a positive correlation between mPRα and p-Akt together with MMP-9. The results confirm that mPRα was a major marker of harmful prognosis and it promoted the expression of MMP-9 during invasion to the local lymph nodes through the pathway of PI3K/Akt. The present study provided a novel therapeutic strategy to inhibit breast cancer growth by preventing mPRα signaling pathway.

Keywords: Invasive breast cancer; MMP-9; Metastasis; mPRα; p-Akt.

MeSH terms

  • Adult
  • Biomarkers, Tumor / metabolism
  • Breast / metabolism
  • Breast / pathology
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Female
  • Humans
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Lymphatic Metastasis / pathology*
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Neoplasm Invasiveness / pathology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Progesterone / metabolism*
  • Signal Transduction / physiology*

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled
  • Receptors, Progesterone
  • membrane progestin receptor alpha, human
  • Phosphatidylinositol 3-Kinases
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 9