Changes in the phenotype of human small cell lung cancer cell lines after transfection and expression of the c-myc proto-oncogene.

Johnson, Bruce E.; Battey, James F.; Linnoila, Ilona; Becker, Kenneth L.; Makuch, Robert W.; Snider, Richard H.; Carney, D.N.; Minna, John D.

doi:10.1172/jci112604

Cited by 88 publications

(32 citation statements)

References 32 publications

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“…6 Oncogene amplification is common in solid tumors and correlates with a poor prognosis for patients with ovarian cancer (HER-2/neu), breast cancer (C-MYC, HER-2/neu), neuroblastoma (N-MYC), or small cell lung cancer (C-MYC). [7][8][9][10] In thyroid cancers, RET amplification correlated with radiation-induced and high-grade malignancy, providing further evidence for the involvement of GIN in tumor progression. 6 P53-binding protein 1 (53BP1) belongs to a family of evolutionarily conserved DDR proteins with C-terminal BRCT domains.…”

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confidence: 98%

Foci formation of P53‐binding protein 1 in thyroid tumors: Activation of genomic instability during thyroid carcinogenesis

Nakashima

Suzuki

Meirmanov

et al. 2007

Intl Journal of Cancer

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Defective DNA damage response (DDR) can result in genomic instability (GIN) and lead to the transformation into cancer. P53-binding protein 1 (53BP1) belongs to a family of evolutionarily conserved DDR proteins. Because 53BP1 molecules localize at the sites of DNA double strand breaks (DSBs) and rapidly form nuclear foci, the presence of 53BP1 foci can be considered as a cytologic marker for endogenous DSBs reflecting GIN. Although it has been proposed that GIN has a crucial role in the progression of thyroid neoplasms, the significance of GIN during thyroid tumorigenesis remains unclear, particularly in patients. We analyzed, therefore, the level of GIN, as detected with immunofluorescence of 53BP1, in 40 cases of resected thyroid tissues. This study demonstrated a number of nuclear 53BP1 foci in thyroid cancers, suggesting a constitutive activation of DDR in thyroid cancer cells. Because follicular adenoma also showed a few 53BP1 nuclear foci, GIN might be induced at a precancerous stage of thyroid tumorigenesis. Furthermore, high-grade thyroid cancers prominently exhibited an intense and heterogeneous nuclear staining of 53BP1 immunoreactivity, which was also observed in radiation-associated cancers and in mouse colonic crypts as a delayed response to a high dose ionizing radiation, suggesting increased GIN with progression of cancer. Thus, the present study demonstrated a difference in the staining pattern of 53BP1 during thyroid carcinogenesis. We propose that immunofluorescence analysis of 53BP1 expression can be a useful tool to estimate the level of GIN and, simultaneously, the malignant potency of human thyroid tumors. ' 2007 Wiley-Liss, Inc.Key words: thyroid cancer; genomic instability; 53BP1; ATM; immunofluorescence DNA damage response (DDR) genes, such as p53, are frequently mutated in human cancer. Defective DDR responses can thus result in genomic instability (GIN) and lead to the transformation of normal cells into cancer cells. Thyroid cancer has been shown to display aneuploidy, one form of GIN. 1 It has been proposed that GIN has a crucial role in the progression of thyroid neoplasms. 2 Thus, transfection of mutant HRAS V12 or mutant BRAF V600E induced GIN in a rat thyroid cell line, manifesting as loss of chromosomal material, mitotic bridge formation and misaligned chromosomes. 3-5 Recently, we found RET oncogene amplification in human thyroid cancers. 6 Oncogene amplification is common in solid tumors and correlates with a poor prognosis for patients with ovarian cancer (HER-2/neu), breast cancer (C-MYC, HER-2/neu), neuroblastoma (N-MYC), or small cell lung cancer (C-MYC). [7][8][9][10] In thyroid cancers, RET amplification correlated with radiation-induced and high-grade malignancy, providing further evidence for the involvement of GIN in tumor progression. 6 P53-binding protein 1 (53BP1) belongs to a family of evolutionarily conserved DDR proteins with C-terminal BRCT domains. 11,12 The ataxia-teleangiactasis mutated (ATM) DDR kinase is well known as a sensor molecule for DNA damage. Both...

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confidence: 98%

Foci formation of P53‐binding protein 1 in thyroid tumors: Activation of genomic instability during thyroid carcinogenesis

Nakashima

Suzuki

Meirmanov

et al. 2007

Intl Journal of Cancer

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“…The experiment was performed twice with similar results. studies demonstrating changes in SCLC proliferation, morphology and biochemistry by activation of these oncogenes (Johnson et al, 1985;Mabry et al, 1983). Previous analysis of two-dimensional gels of iodinated SCLC and NSCLC surface proteins has shown that each of these subtypes of human lung cancer have a distinctive protein phenotype (Goodwin et al, 1983).…”

Section: Discussionmentioning

confidence: 99%

“…H209 is a classic SCLC line that does not express detectable c-myc mRNA. The isolation and characterisation of H209-myc clone E has been previously described (Johnson et al, 1985). Briefly, a c-myc-neo plasmid was constructed by inserting a 12.7 EcoRI human c-myc gene into the EcoRI site of pBR 327.…”

Section: Methodsmentioning

confidence: 99%

“…Johnson and coworkers have demonstrated that stable transfection of multiple copies of the c-myc proto-oncogene leads to the assumption of SCLC-v growth and morphological characteristics by the transfected cells (Johnson et al, 1985). Mabry and his co-investigators have further demonstrated that in SCLC-v, but not classic SCLC cells, insertion of the v-Ha-ras gene could induce features typical of large cell undifferentiated lung carcinoma, a form of NSCLC (Mabry et al, 1983).…”

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Modulation of neuroendocrine surface antigens in oncogene-activated small cell lung cancer lines

Doyle

Mabry²,

Stahel³

et al. 1991

Lung Cancer

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“…This was in contrast to the amplification and expression of N- (19) and L-myc (20) and suggested that c-myc might be respon sible for the altered morphology of this SCLC subclass. In a most recent study, Johnson et al (21) showed that a cell line with classic features altered its morphology and growth prop erties but not its biochemical characteristics into those of the variant subclass upon transfection and expression of c-myc.…”

Section: Introductionmentioning

confidence: 99%

Characterization of two cell lines with distinct phenotypes established from a patient with small cell lung cancer

et al. 1987

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Two small cell lung cancer (SCLC) cell lines were established from pericardia! and pleura! effusions of a patient with histopathologically proven SCLC of the oat cell type. Chemotherapy was administered without response during the 148-day period prior to the establishment of the first cell line, SCLC-22H, and some of the same drugs were admin istered in the 15 days prior to the establishment of the second cell line, SCLC-21H. Both cell lines differed markedly in their biochemical, kinetic, and morphological properties. Although the biomarkers i -Dopa decarboxylase, bombesin, carcinoembryonic antigen, and neurotensin were detectable in SCLC-22H, they were undetectable or low in SCLC-21H. The population doubling time was twice as fast and the colony forming efficiency higher in S( IX -2111 than in SCLC-22H. They both expressed high concentrations of the SCLC marker enzymes neuronspecific enolase and the creatine kinase isoenzyme BB and showed no significant differences in their chromosomal characteristics, c-myc was amplified and expressed in both cell lines, and SCLC-21H had an additional rearrangedand amplified EcoKl c-myc fragment. Morpholog ical differences were apparent in liquid culture, cytology, and xenograft histology, SCLC-21H grew much more loosely than SCLC-22H, and had more prominentnucleoli and more abundantcytoplasm. Ultrastructurally dense core granules were present in both cell lines. SCLC-21H thus expressed properties of the variant cell type of SCLC, whereas SCLC-22H had mixed classic/variant features. An in viro progression of the patient's tumor from a pure small cell to a mixed small cell/large cell morphology could be demonstrated, which suggests that cell line SCLC-22H represents a cell type characteristic for the transitional phase of the tumor. The features of this cell line therefore define a new subclass of SCLC called transitional cell type. SCLC-22H may be of use to study the mechanisms involved in the classic to variant transition, which probably has a considerable impact on the prognosis and response to therapy.

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Changes in the phenotype of human small cell lung cancer cell lines after transfection and expression of the c-myc proto-oncogene.

Cited by 88 publications

References 32 publications

Foci formation of P53‐binding protein 1 in thyroid tumors: Activation of genomic instability during thyroid carcinogenesis

Foci formation of P53‐binding protein 1 in thyroid tumors: Activation of genomic instability during thyroid carcinogenesis

Modulation of neuroendocrine surface antigens in oncogene-activated small cell lung cancer lines

Characterization of two cell lines with distinct phenotypes established from a patient with small cell lung cancer

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