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Rivista di Biologia Molecolare e Biotecnologie

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Minerva Biotecnologica 2001 December;13(4):269-80

lingua: Inglese

Use of the micro­ar­rays to ­study the mech­a­nism of ­action of new anti­can­cer ­drugs

Marchini S. 1, Chiorino G. 2

1 Molec­u­lar Phar­ma­col­o­gy ­Unit, Depart­ment of Oncol­o­gy, “Mario ­Negri” Insti­tute for Phar­mac­o­log­i­cal ­Research, ­Milan (Ita­ly);
2 Labor­a­to­ry of Can­cer Phar­ma­cog­e­nom­ics, “Edo Tem­pia” Foun­da­tion, SEN­DO, Biel­la (Ita­ly)


Micro­ar­rays are a new prom­is­ing ­tool for ­high through­put anal­y­sis of dif­fer­enc­es in ­gene expres­sion pro­file. Micro­ar­ray tech­nol­o­gy has ­been found­ed on a num­ber of impor­tant tech­ni­cal devel­op­ments ­that ­have ­emerged ­over the ­last ­three ­decades: micro­blot­ting, PCR, and the avail­abil­ity of ten of thou­sands of ­sequenced ­cDNA and EST ­clones ­from the ­human gen­o­me pro­ject. The abil­ity to car­ry out inves­ti­ga­tions on ­genome ­wide ­scale is deep­ly rev­o­lu­tion­is­ing dif­fer­ent ­area of molec­u­lar med­i­cine; ­this is ­because chang­es in the molec­u­lar phe­no­type of a ­cell to exter­nal stim­u­li ­should be reflect­ed by its tran­scrip­tion­al pro­file. In a broad­er ­sense, ­gene expres­sion can poten­tial­ly pro­vide infor­ma­tion ­about bio­chem­i­cal and bio­log­i­cal path­ways or reg­u­la­to­ry mech­a­nism of the ­cell. In the ­present chap­ter we ­will ­describe the two ­main ­types of micro­ar­rays com­mer­cial­ly avail­able and ­will dis­cuss two appli­ca­tions of ­this tech­nol­o­gy. ­That is, the char­ac­ter­isa­tion, ­from a molec­u­lar ­point of ­view, of the mech­a­nism of ­action of new prom­is­ing anti­can­cer ­agents and the ­gene expres­sion pro­fil­ing of two ­human ovar­ian can­cer ­cell ­lines ­stably trans­fect­ed ­with the p73α ­cDNA. We ­will ­also ­present and dis­cuss ­some top­ics relat­ed to the anal­y­sis of ­gene expres­sion ­data. ­This is ­another impor­tant fea­ture of the micro­ar­ray tech­nol­o­gy and con­sists of dif­fer­ent ­steps: ­data acqui­si­tion, ­image anal­y­sis, def­i­ni­tion of inten­sity sig­nal, nor­mal­isa­tion of expres­sion ­ratios, com­par­i­son of rep­li­cates, clas­sifi­ca­tion of ­gene expres­sion pro­files, etc. Par­tic­u­lar ­stress is ­laid on the impor­tance of ­doing rep­li­cates, ­since ­there are ­many sourc­es of var­i­abil­ity and ­this is the ­only ­mean to ­obtain sta­tis­ti­cal­ly sig­nif­i­cant ­results.

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