Comparison of features of human breast cancer cell lines and their corresponding tumors.
Although human tumor-derived cell lines play an important role in the investigation of cancer biology and genetics, there is no comprehensive study comparing tumor cell line properties with those of the individual tumors from which they were derived. We compared the properties of a series of 18 human breast cancer cell lines that were cultured for a median period of 25 months (range, 9-60 months) and their corresponding archival tumor tissues. We compared morphological characteristics, ploidy, and immunohistochemical expression of estrogen receptors, progesterone receptors, and HER2/neu and p53 proteins. For 17 of these cases, we also tested for allelic losses at 18 chromosomal regions frequently deleted in breast tumors using 51 polymorphic microsatellite markers, and we determined the TP53 gene mutation status in exons 5 to 10. There was an excellent correlation between the breast tumor cell lines and their corresponding tumor tissues for morphological features (100%); presence of aneuploidy (87%); immunohistochemical expression of estrogen receptors (87%), progesterone receptors (73%), and HER2/neu (93%) and p53 proteins (100%); allelic loss at all of the chromosomal regions analyzed (82-100% concordance); and TP53 gene mutations (75%). The same parental allele was lost in 279 (99%) of 281 of the comparisons of allelic losses. The fractional allelic loss indices (a reflection of the total allelic loss) of the cell lines and their corresponding tumor tissues were identical or similar in 15 (88%) of 17 paired comparisons. Although our previous studies (A. Gazdar et al., Int. J. Cancer, in press) indicated that only a subset of primary breast carcinomas that have several features indicative of advanced tumors with poor prognosis can be successfully cultured, the cell lines retain the properties of their parental tumors for lengthy culture periods and, thus, provide suitable model systems for biomedical studies.
Wistuba
I I
II
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas 75235-8593, USA.
Behrens
C
C
Milchgrub
S
S
Syed
S
S
Ahmadian
M
M
Virmani
A K
AK
Kurvari
V
V
Cunningham
T H
TH
Ashfaq
R
R
Minna
J D
JD
Gazdar
A F
AF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008875:Middle Aged; D011003:Ploidies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D013997:Time Factors; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D004273:DNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53