So far PP1γ2 had been known as a testis specific isoform of Protein Phosphatase-1, for the first time we have identified the expression of PP1γ2 in cancerous cells and claimed PP1γ2 as a novel CTA biomarker. Unique sequence specific to PP1γ2 can be used as precise immunogen to raise the antibodies specific to PPγ2. This study will also be helpful to develop a novel diagnostic strategy to detect early stages of cancer. Such CTAs can emerge to be potentially reliable targets for immunotherapy of cancer because of their limited expression in normal tissues. More particularly, the present invention relates to Genes expressed both in normal testis as well as in malignancies (Cancer/ Testis associated genes – CTA) and these proteins have become the most extensively studied antigen group in the field of tumor immunology.
Our results illustrate the role of PP1γ2 in cell division during tumorigenesis. The aim of the current study is to evaluate the clinical utility of PP1γ2 expression and evaluate the humoral immune response in cancer patients. We demonstrated the expression of PP1γ2 in various cancer cell lines as well as some biopsy samples of cervical cancer patients through various techniques including RT-PCR, Western blotting and immunolocalization, which confirmed the existence of PP1γ2 isoform at both transcript as well as protein level in cancerous cells. Immuno-fluorescence of HeLa Cells (Cervical cancer cell line) with PP1γ2 specific antibodies revealed the spatio-temporal localization of the protein in the nucleus of the mononuclear cells, which was redistributed to the spindle poles of the dividing cells. Cells were also induced with a known cancer drug taxol to find more dividing as well as multipolar arrested cells and the localization of PP1γ2 on the spindle poles of these induced cells was confirmed again. Silencing of PP1γ2 through siRNA in HeLa cells, increased the S9 phosphorylation of GSK3β and demonstrated GSK3β as a substrate of PP1γ2. Increased phosphorylation of GSK3β inactivates this Kinase as well as it’s downstream signalling, which itself is a known fact for the cancer treatment.
The present invention further relates to be used potentially in targeting tumour cells specifically which express this particular protein. Our findings will be explored in early stage of cervical cancer, if a substantial number of patients exhibit the PP1γ2 expression and generate antibodies, supporting its potential role in early detection and diagnosis of cervical cancer. Furthermore, these findings will provide leads for future development of non-invasive therapeutic techniques. The present finding relates to an antibody against the precise immunogen containing a part of Serine Threonine Protein phosphatase1- Gamma 2 (PP1γ2) useful as a biomarker for cancer. Further studies will help in targeting tumour cells specifically which express this particular protein and will also be helpful to develop a novel diagnostic strategy to detect early stages of cancer. Such CTAs can emerge to be potentially reliable targets for immunotherapy of cancer because of their limited expression in normal tissues. HPV prevalence through molecular techniques in the clinical samples will also be correlated with the progression of cervical cancer and the expression of cancer biomarkers.