Affiliation

University of Lahore, Lahore, Pakistan

Corresponding Author

Ahsan Sattar Sheikh, University of Lahore, Lahore- 54000, Pakistan; E-mail: assheikh@bzu.edu.pk

Citation

Sheikh, A.S., et al. Dynamics of Akt Isoforms and Role of Immune Evader (RCAS 1) in Different Grades of Breast Cancer Tissues in Pakistani Women. (2018) Int J Cancer Oncol 5(1): 16- 25.

Copy rights

© 2018 Sheikh, A.S. This is an Open access article distributed under the terms of Creative Commons Attribution 4.0 International License.

Keywords

Abstract

  Breast Cancer (BC) is the leading cause of death among females. It has been documented that Akt isoforms and kRaS control the proliferative pathways in most cancer including BC. To address the issue of breast cancer signaling through mRNA quantification along with proteins quantifications in Akt pathway by microbead assay.
  A total of 42 specimens were selected from a pool of samples representing nearly all Bloom’s Richardson’s grades tissues (Normal, Hyperplasia, Ductal in situ Carcinoma, Grade I, Grade II and Grade III). No Grade IV sample was available. Total of 8 genes (Akt 1, Akt 2, Akt 3, p53, RCAS 1, Bcl 2, BclxL, and Mcl 1) and 11 proteins in PI3K / Akt - mToR pathway were assayed simultaneously using microbead BioPlex™ assay. Results on quantification of RCAS 1 gene (Immune Evader) indicates its significance by increased quantities to help to evade the breast cancer cells to distant places to metastasize in the body. Data obtained on Akt isoforms (Akt 1, Akt 2, Akt 3) show that all three play significant role in the progression of breast cancer. Our data indicate that in advance grades (grade II and III) Akt 3 along with Akt 1 act as oncogenes. Here we propose that Akt1 and Akt 3 appear to be involved in cellular growth/proliferation and angiogenesis/invasion respectively. Bioinformatics modeling have shown that the conformation of Akt 3 differs from Akt 1 and Akt 2 in PH domain that interacts to surface membrane from inner side.
  Based on our data, we conceived that roles of all three Akt isoforms in growth, hypertrophy, epithelial mesenchymal transition (EMT), adhesion, and metastasis been highlighted. As reported in other cancers, Akt 3 appears to be involved in the phosphorylation of VEGF and Integrin family proteins, thereby facilitating invasion and metastasis in the aggressive stages of breast cancer. We propose a model with dynamics of Akt and RCAS 1 for metastasis.