Cancro da mama: a importância de isoformas da proteína tirosina fosfatase

A proteina tirosina fosfatase de baixo peso molecular tem sido associada à tumorigénese e progressão tumoral. No entanto, o seu papel permanece controverso. Neste estudo demonstramos que o papel controverso desta proteína pode dever-se à inexistência de estudos focados nas suas duas principais isoformas, fast e slow. A expressão diferencial destas isoformas deve ser tida em conta quando se estuda a LMW-PTP no contexto tumoral, nomeadamente no cancro da mama. Os nosso resultados evidenciam o papel destas isoformas da LMW-PTP no cancro da mama.

Autores e afiliações:
Irina Alho1,2, Luís Costa2,3, Manuel Bicho1 and Constança Coelho1
1Genetics Laboratory, Lisbon Medical School, Lisbon, Portugal;
2Institute of Molecular Medicine, Lisbon, Portugal;
3Medical Oncology Department, Oncology Division,
Santa Maria Hospital, Hospital, North Lisbon Hospital Center, Lisbon, Portugal

Abstract:
Background: Low molecular weight protein tyrosine phosphatase (LMW-PTP) is a polymorphic protein with two major isoforms whose role in tumorigenesis is currently controversial. Materials and Methods: We characterized LMW-PTP genotype, isoform expression and activity in six different human breast cancer epithelial cell lines (ZR75, MDA-MB-231, MDA-MB-231BO, MCF7, MDA-MB-231BO2, MDA-MB-435) and compared them with MCF10A, a normal breast epithelial cell line. Results: mRNA expression of the slow isoform was increased in almost all breast cancer cell lines and that of the fast isoform was reduced (p<0.05) in all breast cancer cell lines. Regarding enzymatic activity, only MCF7 had significantly lower (p<0.05) LMW-PTP activity compared to MCF10A. Conclusion: Since these are novel and previously unreported findings, we propose that the differential expression of LMW-PTP fast and slow isoforms suggests their opposite roles in the tumorigenic process, with the fast isoform being anti-oncogenic and the slow isoform being oncogenic.

Revista:
Anticancer Research

Link:
http://ar.iiarjournals.org/content/33/5/1983.long