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Ahmed MM , Sheldon D , Fruitwala MA , Venkatasubbarao K , Lee FY , Gupta S , Wood C , Mohiuddin M , Strodel WE
Downregulation of PAR-4, a pro-apoptotic gene, in pancreatic tumors harboring K-ras mutation
International Journal of Cancer. 2008 Jan;122(1) :63-70
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Oncogenic ras is known to inhibit cell death and growth inhibitory genes and activate prosurvival genes. Proapoptotic gene PAR-4, has been found to be downregulated by oncogenic ras. Since pancreatic tumors harbor a high incidence of K-ras point mutations, we hypothesized that oncogenic K-ras might influence the function and expression of PAR-4. PAR-4 expression levels were analyzed in 4 established pancreatic tumor cell lines, 10 normal pancreatic tissues, 44 frozen tumor tissues and 25 paraffin-embedded pancreatic adenocarcinoma samples by Real Time RT-PCR, Western blot analysis and immunohistochemistry. K-ras mutational status was analyzed by allele-specific oligonucleotide-hybridization. Expression levels of PAR-4 were correlated with the K-ras mutational status and clinical characteristics. Further, modulation of endogenous PAR-4 was tested by transiently expressing oncogenic ras in a wild-type K-ras pancreatic cancer cell line, BxPC-3. Three cell lines with K-ras mu!
Ahmed, Mansoor M. Sheldon, David Fruitwala, Mushtaq A. Venkatasubbarao, Kolaparthi Lee, Fun Y. Gupta, Seema Wood, Craig Mohiuddin, Mohammed Strodel, William E. WILEY-LISS