PI3K Pathway

سال انتشار: 1395
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 335

نسخه کامل این مقاله ارائه نشده است و در دسترس نمی باشد

استخراج به نرم افزارهای پژوهشی:

لینک ثابت به این مقاله:

شناسه ملی سند علمی:

NASTARANCANSER02_127

تاریخ نمایه سازی: 22 دی 1396

چکیده مقاله:

Phosphatidylinositol-3 kinases, PI3Ks, is a family of lipid kinases that it causes phosphorylateinositol phospholipids to make signal passway, that regulators many essential cellular functions,consist of cell survival, growth, and differentiation in cells.PI3K pathway and cancer: a- Somaticchanging:1- Genetic mutations/loss of function: one of most reform genetic can activate thePI3K/AKT signaling, and the second is inactivation of the PTEN: protein truncations, missensemutations, Transcriptional repression and epigenetic silencing. It can be deleted by two formswhich are heterozygous and Homozygous loss. 2- Genetic amplification of PI3K: These mutationscause various human tumors consist of breast, colon, and endometrial cancers and glioblastoma.Mutation in PIKCA genes (encode p110α) is usual mutation, which intensification p110α activation.So PI3K pathway will be hyperactivated. 3- AKT overexpression: overexpression AKT1,2 causedifferent cancer. AKT1: breast, colorectal, endometrial, and ovarian cancers. AKT2: colorectalcancers and metastases.b- Activate RTK: Mutation in different RTK result different cancer:epithelial growth factor receptor (EGFR) cause lung cancers and human epidermal growth factorreceptor 2 (HER2) mutations cause breast cancers. Study of this pathway is important for tumordevelopment and tumor’s treatment. Targeted agents are designed for PI3K/Akt signal region. Fourimportant classes are: dual PI3K-mTOR inhibitors, PI3K inhibitors, AKT inhibitors, mTOR catalyticsite inhibitors. Base on function and structure there are three classes of PI3Ks grouped (classI,II,III). Most of human cancer in PI3K pathway related to Class I PI3Ks, which is heterodimersconsists of an adaptor/regulatory subunit (p85) and a catalytic subunit (p110). Growth factor bindsto receptor tyrosine kinases (RTKs) after that phosphorylate it. This process releases inhibitor fromthe p110. Thereby PI3K localize in the plasma membrane, after that PI3K phosphorylatephosphatidylinositol4,5-bisphosphate (PI[4,5]P2), shift it to PIP3. Further PI3K is stimulated byactivated Ras, which binds p110 directly. The p110 can also be activated by G-protein_ receptorscomplex. PTEN is a tumor suppressor phosphatase that dephosphoryates PIP3 to PIP2, it isconversely action PI3K and finish PI3K signal pathway. PIP3 transfer intracellular signaling to cellmolecular by binding signaling proteins such as AKT (AGC kinase family). AKT promotes severalacts in cells: AKT can inhibit proapoptotic Bcl-2 family that causes cell survival. AKT increasetranscription of antiapoptotic and prosurvival genes. AKT Phosphorylate Mdm2 to genderapoptosis and AKT can decrease proteins of cell death-promoting. AKT relieves inhibit of the rheb,so reduce protein.

نویسندگان

Mehri Soltani-Bayat

Department Of Biology, Faculty Of Sciences, Hakim Sabzevari University, Sabzevar, Iran

Madjid Momeni-moghadam

Department Of Biology, Faculty Of Sciences, Hakim Sabzevari University, Sabzevar, Iran