Transcript Diapositiva 1

AUTOPHAGY IN COLORECTAL CANCER:
PRELIMINARY OBSERVATIONS
Lorenzo Marasà1, Anna Merendino2, Francesca Rappa1, Fabio Bucchieri2, Salvatore
Marasà1, Antonio Giacalone1, Francesco Cappello2, Giovanni Zummo2.
C.O.U. of Pathologic Anatomy, ARNAS-Civico Hospital, Palermo, Italy.
2 Department of Experimental Medicine, Human Anatomy Section, University of Palermo, Italy.
1
Autophagy is a catabolic process involving the degradation of cellular
components through the autophagosome pathway. This highly-regulated
process plays a pivotal role in tissutal differentiation and homeostasis (1).
Moreover, it may be important in cancer development and progression as well
as in determining the response of tumor cells to anticancer therapy (2).
During autophagic degradation, cytosolic proteins and/or organelles are first
sequestered within double membrane vesicles called autophagosomes, which
are then fused to the lysosome.
Available at http://hopes.stanford.edu/treatmts/pbuildup/f_h03autophagy.jpg
The complex Beclin1-PI(3)KC3 promotes autophagy and suppresses the
proliferation and tumorigenicity of human colon cancer cells.
UVRAG protein activates the Beclin1-PI(3)KC3 complex and promotes the catabolic
process. The regulation of the Beclin 1-PI3KC3 complex lipid kinase activity is a critical
element in the autophagy signaling pathway(6).
Aims
With the present work we are studying some molecules
involved in the regulation of autophagic process in a
series of colorectal cancers.
Materials and methods
Immunohistochemistry for:
- Beclin-1 (ABGENT, cat. No. AP1818a, 1:50)
- UVRAG (ABGENT, cat. No. AP1850b, 1:50)
- mTOR (Cell Signaling, # 2983, 1:50)
-Phospho-mTOR (Cell Signaling, # 2976, 1:50)
- Kit: Ventana, iview™DAB
- Equipment: Ventana BenchMark XT IHC/ISH
Preliminary results
Beclin-1 is downregulated in
cytoplasm of tumoral cells,
compared to normal epithelial ones.
Preliminary results
UVRAG is also
downregulated in cytoplasm
of tumoral cells, compared
to normal epithelial ones.
Preliminary results
mTOR is downregulated in
cytoplasm of tumoral cells
Preliminary results
ph-mTOR* is overexpressed
in tumoral cells.
*mTOR is a negatively regulator of autophagy, the phosphorilation
active mTOR
Conclusions
•Our results for Beclin-1 are in contrast with what showed by other groups (3,4), but
in agreement with other studies conducted in other types of neoplasms (5).
•By contrast, no data are available concerning UVRAG expression in colorectal
cancers.
•This study could add important information concerning the role of this molecules in
colon cancer development and progression as well as in determining the response
of tumor cells to anticancer therapy (2).
References
1. Lerena C et al., Curr Mol Med. 2008;8:92.
2. Hippert MM et al., Cancer Res. 2006;66:9349.
3. Li BX et al., Autophagy. 2009;5:303.
4. Ahn CH et al., APMIS. 2007;115:1344.
5. Liang XH et al., Nature. 1999;402:672.
6. Liang C et al., Autophagy 2007; 3:69.