Abstract
A cell line designated CUMO-2 has been established from an undifferentiated ovarian carcinoma. The s.c. injection of cells into nude mice gave rise to fast-growing tumors, while the i.p. route induced a peritoneal carcinomatosis with ascites. Histopathologically, the transplanted s.c. tumors closely resembled the original tumor, but tumors developed in the peritoneal cavity were highly anaplastic. The epithelial nature of the cells was confirmed by ultrastructural analysis. Sequential cytogenetic analyses on early and late passages revealed highly aneuploid tumor cells with consistent structural aberrations of chromosomes 1, 3, 8 and 11. CUMO-2 cells were found to produce CA 125 in vitro and in vivo. Cytosol estrogen receptor (ER) was found but progesterone receptor (PR) was not measured. HLA typing indicated the presence of DR8 and DQw4. A gonadotropin-releasing hormone (Gn-RH) analog inhibited cell growth and Gn-RH receptor mRNA was detected by reverse transcription/polymerase chain reaction in this cell line. Administration of transforming growth factor β1 inhibited both cell growth and c-myc mRNA expression. This cell line demonstrated a conformational band shift in exon 7 of thep53 gene. It was a frameshift mutation.
Key Words: Human ovarian cancer, Permanent cell line, Cytogenetics, Transforming growth factor, Tumor, suppressor gene
Abbreviations
- Gn-RH
gonadotropin-releasing hormone
- ER
estrogen receptor
- PR
progesterone receptor
- RT-PCR
reverse transcription/polymerase chain reaction
- TGF
transforming growth Factor
- SSCP
Single-strand conformation polymorphism
- MTT
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenytetrazolium bromide
Footnotes
This work was supported by a grant from the Korea research foundation, 1990
References
- Alnemri ES, Fernandes TF, Haldar S, Croce CM, Litwack G (1992) Involvement ofBCL-2 in glucocorticoid-induced apoptosis of human pre-B-leukemias. Cancer Res 52:491–495 [PubMed] [Google Scholar]
- Askew DS, Ihle JN, Cleveland JL (1993) Activation of apoptosis associated with enforced Myc expression in myeloid progenitor cells is dominant to the suppression of apoptosis by interleukin-3 or erythropoietin. Blood 82:2079–2087 [PubMed] [Google Scholar]
- Aure JC, Hoeg K, Kolstad P (1971) Clinical and histologic studies of ovarian carcinoma: long-term follow-up of 990 cases. Obstet Gynecol 37:1–9 [PubMed] [Google Scholar]
- Buller RE, Niemann T, Connor JP, Squatrito RC, Skilling JS, Anderson B (1995) Isolation and preliminary characterization of an ovarian carcinoma cell line from a patient with familial ovarian cancer. Gynecol Oncol 56:39–44 [DOI] [PubMed] [Google Scholar]
- Buchman VL, Chumakov PM, Ninkina NN, Samarian OP, Georgiev GP (1988) A variation in the structure of the protein-coding regions of the humanp53 gene. Gene 70:245–252 [DOI] [PubMed] [Google Scholar]
- Chi L, Zhou W, Prikhozhan A, Flanagan C, Davidson JS, Golembo M, Illing N, Millar RP, Sealfon SC (1993) Cloning and characterization of the human GnRH receptor. Mol Cell Endocrinol 91:R1–5 [DOI] [PubMed] [Google Scholar]
- Eidne KA, Flanagan CA, Harris NS, Millar RP (1987) Gonadotropin-releasing hormone (Gn-RH)-binding sites in human breast cancer cell lines and inhibitory effects of Gn-RH antagonists. J Clin Endocrinol Metab 64:425–432 [DOI] [PubMed] [Google Scholar]
- Fekete M, Zalatnai A, Comaru-Schally AM, Schally AV (1989) Membrane receptors for peptides in experimental and human pancreatic cancers. Pancreas 4:521–528 [DOI] [PubMed] [Google Scholar]
- Fuchtner C, Emma DA, Manetta A, Gamboa G, Bernstein R, Liao SY (1993) Characterization of a human ovarian carcinoma cell line: UCI 101. Gynecol Oncol 48:203–209 [DOI] [PubMed] [Google Scholar]
- Hamilton TC, Young RC, McCoy WM, Grotzinger KR, Green JA, Chu EW, Whang-Peng J, Rogan AM, Green WR, Ozols RF (1983) Characterization of a human ovarian carcinoma cell line (NIH:OVCAR-3) with androgen and estrogen receptors. Cancer Res 43:5379–5389 [PubMed] [Google Scholar]
- Imai A, Ohno H, Iida K, Fuseya T, Furui T, Tamaya T (1994) Presence of gonadotropin-releasing hormone receptor and its messenger ribonucleic acid in endometrial carcinoma and endometrium. Gynecol Oncol 55:144–148 [DOI] [PubMed] [Google Scholar]
- Kimura S, Maekawa T, Hirakawa K, Murakami A, Abe T (1995) Alteration of c-myc expression by antisense oligodeoxynucleotides enhance the induction of apoptosis in HL-60 cells. Cancer Res 55:1379–1384 [PubMed] [Google Scholar]
- Knudson AG (1993) Antioncogenes and human cancer. Proc Natl Acad Sci USA 90:10914–10921 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kunzmann R, Holzel P (1987) Karyotype alterations in human ovarian carcinoma cells during long term cultivation and nude mouse passage. Cancer Genet Cytogenet 28:201–212 [DOI] [PubMed] [Google Scholar]
- Marsh GES, Bodmer JG (1992) HLA class II nucleotide sequences. In: Jsuji K, Aizawa M, Sasazuki T (eds) Proceedings of the Eleventh International Histocompatibility Workshop and Conference, vol I. Oxford Science Publications, Oxford, pp 32–62 [Google Scholar]
- Mulder KM, Levine AE, Hernandez X, McKnight MK, Brattain DE, Brattain MG (1988) Modulation of c-myc by transforming growth factor-β in human colon carcinoma cells. Biochem Biophys Res Commun 150:711–716 [DOI] [PubMed] [Google Scholar]
- Olah E, Balogh E, Kovacs I, Kiss A (1989) Abnormalities of chromosome 1 in relation to human malignant diseases. Cancer Genet Cytogenet 43:179–194 [DOI] [PubMed] [Google Scholar]
- Panani A, Ferti-Passantonopoulou A (1985) Common manker chromosomes in ovarian cancer. Cancer Genet Cytogenet 16:65–71 [DOI] [PubMed] [Google Scholar]
- Pathak S (1976) Chromosome banding techniques. J Reprod Med 17:25–28 [PubMed] [Google Scholar]
- Pietenpol JA, Holt JT, Stein RW, Moses HL (1990) Transforming growth factor β-1 suppression of c-myc gene transcription: role in inhibition of keratinocyte proliferation. Proc Natl Acad Sci USA 87:3758–3762 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Qayum A, Gullick W, Clayton RC, Sikora K, Waxman J (1990) The effects of gonadotropin releasing hormone analogues in prostate cancer are mediated through specific tumor receptors. Br J Cancer 62:96–99 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Richadson GS, Scully RE, Nikrui N, Nelson JH (1985) Medical progress: common epithelial cancer of the ovary. N Engl J Med 312:415–424 [DOI] [PubMed] [Google Scholar]
- Roberts AB, Sporn MB (1990) The transforming growth factors-β In: Sporn MB, Roberts AB (eds) Handbook of experimental pharmacology. Peptide growth factors and their receptors, Springer, New York Berlin Heidelberg, pp 419–472 [Google Scholar]
- Saiki RK, Bugawan TI, Horn GT, Mullis KB, Erlich HA (1986) Analysis of enzymatically amplified beta-globin and HLA-DQ alpha DNA with allele specific oligonucleotide probes. Nature 324:163–166 [DOI] [PubMed] [Google Scholar]
- Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz PE, Merino MJ, LiVolsi VA, Lawrence R, MacLusky N, Eisenfeld A (1985) Histopathologic correlations of estrogen and progestin receptor protein in epithelial ovarian carcinomas. Obstet Gynecol 66:428–433 [PubMed] [Google Scholar]
- Sheer D, Sheppard DM, Gorman PA, Ward B, Whelan RDH, Hill BT (1987) Cytogenetic analysis of four human ovarian carcinoma cell lines. Cancer Genet Cytogenet 26:339–349 [DOI] [PubMed] [Google Scholar]
- Slotman B, Rao B (1988) Ovarian carcinoma (review). Anticancer Res 8:417–434 [PubMed] [Google Scholar]
- Smith A, Haaften-Day C, Russel P (1989) Sequential cytogenetic studies in an ovarian cancer cell line. Cancer Genet Cytogenet 38:13–24 [DOI] [PubMed] [Google Scholar]
- Suzuki Y, Sekiya T, Hayashi K (1991) Allele-specific polymerase chain reaction: a method for amplification and sequence determination of a single component among a mixture of sequence variants. Anal Biochem 192:82–84 [DOI] [PubMed] [Google Scholar]
- Wake N, Hreshchyhyn MM, Piver SM, Matsui S, Sandberg AA (1980) Specific cytogenetic changes in ovarian cancer involving chromosomes 6 and 14. Cancer Res 40:4512–4518 [PubMed] [Google Scholar]
- Yaginuma Y, Westphal H (1992) Abnormal structure and expression of thep53 gene in human ovarian carcinoma cell lines. Cancer Res 52:4196–4199 [PubMed] [Google Scholar]
