AUTOPHAGY IN COLORECTAL CANCER: PRELIMINARY OBSERVATIONS

Lorenzo Marasà1, Anna Merendino2, Francesca Rappa1, Fabio Bucchieri2, Salvatore Marasà1, Antonio Giacalone1, Francesco Cappello2, Giovanni Zummo2.

1 C.O.U. of Pathologic Anatomy, ARNAS-Civico Hospital, Palermo, Italy.2 Department of Experimental Medicine, Human Anatomy Section, University of Palermo, Italy.

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).

With the present work we are studying some molecules involved in the regulation of autophagic process in a

series of colorectal cancers.

Aims

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

Materials and methods

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.

mTOR is downregulated in cytoplasm of tumoral cells

Preliminary results

Preliminary results

ph-mTOR* is overexpressed in tumoral cells.

*mTOR is a negatively regulator of autophagy, the phosphorilation active mTOR

•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).

Conclusions

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.

References