Human breast cancer MCF-7 cell line contains inherently drug-resistant subclones with distinct genotypic and phenotypic features

Author(s): Devarajan E, Chen J, Multani AS, Pathak S, Sahin AA, et al.


The resistance of cancer cells to multiple chemotherapeutic agents poses a major problem in the successful treatment of breast cancer. Whether drug resistance is due to changes induced in the drug-exposed tumor cells or represents the selective growth of one or more drug-resistant clones present in the initial tumor remains controversial. Here we provide evidence that the development of multidrug resistance in a human breast cancer cell line (MCF-7) is a result of propagation of an inherently resistant subclone. The drug-resistant MCF-7 (MCF-7/DOX) cells exhibited several phenotypic and genotypic features that were notably distinct from those observed in the parental drug-sensitive (MCF-7/WT) cells. The most striking change was the presence of a full-length functional caspase-3 in MCF-7/DOX cells that was missing in the parental MCF-7/WT cells due to a deletion mutation in the caspase-3 gene. A drug-resistant MCF-7 cell subline (MCF-7/WT/DOX) was established by exposing the MCF-7/WT cells directly to a high dose of doxorubicin and used for determining the phenotypic and genotypic alterations associated with drug resistance. The MCF-7/WT/DOX cells exhibited alterations identical to those of the MCF-7/DOX cells but which were strikingly distinct from the parental MCF-7/WT cell line. These results suggest that drug resistance is an inherent property of some cancer cells that are present in the initial tumor burden and exhibit distinct phenotypic/genotypic alterations.

Similar Articles

Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene

Author(s): Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, et al.

Defective autophagy leads to cancer

Author(s): Edinger AL, Thompson CB

Induction of autophagy and inhibition of tumorigenesis by beclin 1

Author(s): Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, et al.

Protein and mRNA expression of autophagy gene Beclin 1 in human brain tumours

Author(s): Miracco C, Cosci E, Oliveri G, Luzi P, Pacenti L, et al.

Beclin 1 mRNA strongly correlates with Bcl-XLmRNA expression in human hepatocellular carcinoma

Author(s): Daniel F, Legrand A, Pessayre D, Borrega-Pires F, Mbida L, et al.

Beclin 1 gene inhibits tumor growth in colon cancer cell lines

Author(s): Koneri K, Goi T, Hirono Y, Katayama K, Yamaguchi A

Role of autophagy in cancer

Author(s): Mathew R, Karantza-Wadsworth V, White E

Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis

Author(s): Degenhardt K, Mathew R, Beaudoin B, Bray K, Anderson D, et al.

Autophagy is a therapeutic target in anticancer drug resistance

Author(s): Chen S, Rehman SK, Zhang W, Wen A, Yao L, et al.

Tissue transglutaminase inhibits autophagy in pancreatic cancer cells

Author(s): Akar U, Ozpolat B, Mehta K, Fok J, Kondo Y, et al.

Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes

Author(s): Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, et al.

Hallmarks of cancer: the next generation

Author(s): Hanahan D, Weinberg RA

Autophagy triggered by magnolol derivative negatively regulates angiogenesis

Author(s): Kumar S, Guru SK, Pathania AS, Kumar A, Bhushan S, et al.

Pancreatic cancer biology and genetics

Author(s): Bardeesy N, DePinho RA

Down-regulation of caspase 3 in breast cancer: a possible mechanism for chemoresistance

Author(s): Devarajan E, Sahin AA, Chen JS, Krishnamurthy RR, Aggarwal N, et al.

The induction of autophagy by gamma-radiation contributes to the radioresistance of glioma stem cells

Author(s): Lomonaco SL, Finniss S, Xiang C, Decarvalho A, Umansky F, et al.