Protein Changes Typical for Therapy-resistant Cancer Cells Appear in MCF7 Breast Cancer Cultures as Early as One Doubling Time after Chemical Treatment
Abstract:
Presumably any tumor cell population contains concomitantly, therapy-sensitive and therapy-resistant cells in contrast to the opinion, still held by many, that drug resistance develops only after repeated cycles of treatment. To test this hypothesis we selected a breast cancer cell line that under exposure to AGL2592 (Stat3 inhibitor) will result, along a wide concentration range, in steady levels of residual cell counts. MCF7 and T47D breast cancer cell lines showed a low ic50 (0.4 and 0.5 μM, respectively) from which we chose MCF7 because it showed only 10% residual cells compared to 40% in T47D. Proteomes of resistant and untreated MCF7 cells were run on 2D-gels for comparative analysis of protein expression. Calreticulin (CRT) and protein disulfide isomerase (PDI) showed lower abundance in treated cultures. Glycolytic enzymes, enolase1, aldolase A and glyceraldehydes 3 phosphate dehydrogenase (GAPDH) were more abundant and less modified in treated cultures. AGL2529-sensitivity was associated with part of the GAPDH molecules susceptible to cleavage at Ile170 and adenylation between Ile170 and Lys186. The differential profile exhibited by all the above proteins is (according to others) the hallmark of unfavorable prognosis, which suggests that therapy resistant and sensitive MCF7 populations may coexist in this cell line in its pre-selected form.
Benjamin Y. Klein, Suovenir Tachado , Henry Koziel and Hava K. Avraham , 2006. Protein Changes Typical for Therapy-resistant Cancer Cells Appear in MCF7 Breast Cancer Cultures as Early as One Doubling Time after Chemical Treatment. International Journal of Cancer Research, 2: 161-175.
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