Involvement of the Inositol-trisphosphate Receptor in Invasive or Migratory-type Breast Cancers
Involvement of the Inositol-trisphosphate Receptor in Invasive or Migratory-type Breast Cancers
Breast cancer is the leading cause of female cancer and female death by cancer in France.
 Despite the improvement in early detection and therapeutic arsenal, the mortality of this
 cancer remains high with 11 886 deaths estimated in 2012. Breast cancer is most often a
 carcinoma born from the lobular or ductal epithelium and is classified In two main
 categories: non invasive and invasive. Invasive breast cancers account for 75% of the cases.
 They are usually ductal (75%) and more rarely lobular (25%). The cancer cells are then no
 longer circumscribed to the galactophoric canals or glands but have invaded neighboring
 tissues. If they are not treated in time, these cancers can then spread: the cancerous cells
 will then migrate either by the lymphatic vessels to reach the neighboring ganglia or through
 the blood vessels to give metastases in other tissues In the liver, lungs and bones). The
 mortality associated with breast cancer is not due to the growth of the primary tumor but
 rather to the occurrence of metastases. The study of the mechanisms leading to metastatic
 invasion (i.e. migration and invasion) is therefore of considerable importance. The
 development of metastases depends on the acquisition by the cancer cells of various
 capacities including that of being able to migrate, involving a remodeling of the
 cytoskeleton highly dependent on the intracellular calcium (Ca2 +) concentration. Several
 types of signals are able to induce mobilization of Ca2 + from the extracellular medium or
 endoplasmic reticulum (ER) reserves. At the intracellular level, some of these signals are
 generated by inositol (1,4,5) -trisphosphate (IP3) from the activation of G protein-coupled
 receptors or certain receptors with tyrosine kinase activity. Has been shown that the
 expression, activity and regulation of IP3R receptors (IP3Rs) are involved in the cancerous
 processes of many tissues, in particular in the phenomena of proliferation of breast cancer
 cells. Overall, altered expression and / or activity of IP3Rs can be used for the survival,
 growth, proliferation and migration of cancer cells.

 In the laboratory, the investigator showed that regulation of the expression of subtype 3
 (IP3R3) by 17β-estradiol (E2) is involved in the growth of the human mammary cancer line
 MCF-7. E2 triggers the release of Ca2 + in an IP3-dependent mechanism, while prolonged
 exposure to E2 leads to an increase in the expression of IP3R3. At the same time, the
 reduction in the expression of IP3R3 cancels the proliferative effect of E2 on MCF-7 cells.
 More recently, the investigator has established that IP3R3 regulates the proliferation of
 cells of the human MCF-7 mammary cancer cell line via a molecular and functional interaction
 with the Ca2 + -dependent BKCa potassium channel. The determination of IP3Rs, including
 subtype 3, as a mediator / marker of breast carcinogenesis appears to be a major clinical
 issue.
Inclusion Criteria:

 -  CCI / CLI to be operated

 -  Grade SBR 1, 2 or 3

 -  Undifferentiated RE / PR status

 -  HER2 status undifferentiated

 -  Ki 67 indifferent

 -  Metastatic or not

 -  ADP axillary invaded or not

 -  Major Patients

 Exclusion Criteria:

 -  CIC / CIL

 -  Males