pERK, pAkt and pBad: a possible role in cell proliferation and sustained cellular survival during tumorigenesis and tumor progression in ENU induced transplacental glioma rat model.
Gliomas remain to be an unresolved medical problem. Better understanding of complex regulation and key molecules involved in glioma pathology are needed for designing new and effective treatment modalities. Activation of mitogen-activated protein kinase/extracellular signal regulated kinase (ERK) pathway is known to be having a critical role in cell proliferation and differentiation during the invasion and metastasis of the tumor cells. In the present study, N-ethyl N-nitrosourea induced glioma rat model was used to understand the role of ERK1/2 and Akt pathways in the progression of tumor malignancy. Twenty-four glioma rat brains of early (P90) and progressive (P180) stages were used for histological and immunoblot analysis. Results have shown increased levels of activated ERK1/2, activated Akt or protein kinase B, Bcl-2 and pBad in the glioma rats. This study may indicate increased cell proliferation and angiogenesis, mediated through activation of both ERK and Akt pathways along with increased levels of pBad. Further, pAkt and Bcl-2 levels in the progressive stage glioma rats may indicate existence of sustained tumor cell survival signals. Moreover, enhanced pBad levels in tumor may indicate that there are anti-apoptotic mechanisms, further making the malignant cells resistant to apoptosis.
Bhaskara
Vasanth Kumar
VK
Department of Animal Sciences, School of Life Sciences, University of Hyderabad, PO Central University, Hyderabad, Andhra Pradesh, 500046, India.
Sundaram
Challa
C
Babu
Phanithi Prakash
PP
D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005038:Ethylnitrosourea / Q000633:toxicity*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005910:Glioma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D010766:Phosphorylation; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D051025:bcl-Associated Death Protein / Q000378:metabolism*
D000477:Alkylating Agents; D051025:bcl-Associated Death Protein; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D005038:Ethylnitrosourea