Immortalized and tumorigenic adult human prostatic epithelial cell lines: Characteristics and applications part I. Cell markers and immortalized nontumorigenic cell lines

Several immortalized and malignant adult human prostatic epithelial cell lines have recently been developed. The three most widely used carcinoma cell lines, DU‐145, PC‐3, and LNCaP, developed between 1977 and 1980, have greatly contributed to our present understanding of prostate cancer. Before a cell line can be accepted as having prostatic epithelial origin, some basic characteristics must be established. Expression of specific cytokeratins, but absence of desmin and factor VIII, should be first determined to establish epithelial origin. Responsiveness to androgens and expression of androgen receptor and prostate specific antigen should be examined under stringent culture conditions to establish prostatic epithelial origin. Response to growth factors and expression of their receptors facilitates further characterization of cell behavior. Cell lines immortalized by human papillomaviruses (HPVs) are of special interest because HPVs are involved in a variety of anogenital cancers and may also play a role in prostate carcinogenesis. Malignant transformation of HPV‐18 immortalized cells with the ras oncogene provides cell systems for investigating the multistep process of carcinogenesis. Each cell line has some unique characteristics, whether it arose directly from a carcinoma or resulted from immortalization with simian virus 40 (SV40) or HPV or was transformed in vitro by oncogenes. Comparisons of these characteristics should facilitate elucidation of the mechanisms involved in initiation, promotion, and progression of prostate cancer. These cell lines will further serve as useful models for investigating tumor progression, invasion, metastasis, new therapeutic strategies, drug resistance, and its reversal and chemoprevention. This review will be published in three parts and will summarize cell markers necessary for characterization, as well as the characteristics and some applications of the immortalized as well as malignant adult human prostatic epithelial cell lines. Part 1 deals with cell markers and the immortalized, nontumorigenic cell lines. © 1996 Wiley‐Liss, Inc.

[1]  G. Murphy,et al.  Measurements of prolactin and androgens in patients with prostatic diseases. , 1980, Oncology.

[2]  Jean D. Wilson,et al.  Androgen increases androgen receptor protein while decreasing receptor mRNA in LNCaP cells , 1991, Molecular and Cellular Endocrinology.

[3]  J. Veldscholte,et al.  Regulation of growth of LNCaP human prostate tumor cells by growth factors and steroid hormones , 1991, The Journal of Steroid Biochemistry and Molecular Biology.

[4]  P. Sluss,et al.  Insulin‐like growth factor I: Action and receptor characterization in human prostate cancer cell lines , 1993, The Prostate.

[5]  M. Lucia,et al.  The human prostatic carcinoma cell line LNCaP expresses biologically active, specific receptors for 1 alpha,25-dihydroxyvitamin D3. , 1992, Cancer research.

[6]  W. Fair,et al.  Expression of the prostate-specific membrane antigen. , 1994, Cancer research.

[7]  N. Hay,et al.  Increased androgen receptor activity and altered c-myc expression in prostate cancer cells after long-term androgen deprivation. , 1994, Cancer research.

[8]  L. F. Fajardo.  Special Report The Complexity of Endothelial Cells: A Review , 1989 .

[9]  L. Truong,et al.  The diagnostic utility of desmin. A study of 584 cases and review of the literature. , 1990, American journal of clinical pathology.

[10]  O. Cussenot,et al.  Immortalization of human adult normal prostatic epithelial cells by liposomes containing large T-SV40 gene. , 1991, The Journal of urology.

[11]  K. Bauer,et al.  Reconstituted basement membrane promotes morphological and functional differentiation of primary human prostatic epithelial cells , 1991, The Prostate.

[12]  H. Bojar,et al.  The synthetic androgen mibolerone induces transient suppression of the transformed phenotype in an androgen responsive human prostatic carcinoma cell line: Das synthetische Androgen Miboleron induziert eine transiente Suppression des transformierten Phänotyps in einer Androgen‐abhängigen menschliche , 1990, Andrologia.

[13]  E. Berns,et al.  Androgen‐dependent growth regulation of and release of specific protein(s) by the androgen receptor containing human prostate tumor cell line LNCaP , 1986 .

[14]  J. Rhim,et al.  Altered growth-regulation of prostatic epithelial-cells by human papillomavirus-induced transformation. , 1995, International journal of oncology.

[15]  G. Jenster,et al.  The androgen receptor in LNCaP cells contains a mutation in the ligand binding domain which affects steroid binding characteristics and response to antiandrogens , 1992, The Journal of Steroid Biochemistry and Molecular Biology.

[16]  P. Walsh,et al.  Immunohistochemical study of androgen receptors in metastatic prostate cancer. Comparison of receptor content and response to hormonal therapy , 1991, Cancer.

[17]  M. Webber,et al.  Androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18. , 1997, Carcinogenesis.

[18]  D. Williams,et al.  Prostate specific antigen and androgen receptor induction and characterization of an immortalized adult human prostatic epithelial cell line. , 1996, Carcinogenesis.

[19]  G. Miller,et al.  A serum‐free defined medium capable of supporting growth of four established human prostatic carcinoma cell lines , 1994, The Prostate.

[20]  H. Keer,et al.  Elevated transferrin receptor content in human prostate cancer cell lines assessed in vitro and in vivo. , 1990, The Journal of urology.

[21]  K. Watt,et al.  Human prostate-specific antigen: structural and functional similarity with serine proteases. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[22]  M. Webber,et al.  Prostate-specific antigen, a serine protease, facilitates human prostate cancer cell invasion. , 1995, Clinical cancer research : an official journal of the American Association for Cancer Research.

[23]  C. Boring,et al.  Cancer statistics, 1990 , 1990, CA: a cancer journal for clinicians.

[24]  M. Mesiti,et al.  Prostate Long‐Term Epithelial Cell Lines. Biological and Biochemical Features a , 1990, Annals of the New York Academy of Sciences.

[25]  P. Weijerman,et al.  Lipofection-mediated immortalization of human prostatic epithelial cells of normal and malignant origin using human papillomavirus type 18 DNA. , 1994, Cancer research.

[26]  Y. Katsuoka,et al.  Autoradiographic and cytochemical localization of androgen in human prostatic cancer cell lines. , 1986, Urology.

[27]  A. Kirschenbaum,et al.  The effect of dihydrotestosterone and culture conditions on proliferation of the human prostatic cancer cell line LNCaP , 1992, Steroids.

[28]  A. Brinkmann,et al.  The human androgen receptor is a 110 kDa protein , 1989, Molecular and Cellular Endocrinology.

[29]  G. Mills,et al.  Androgen-induced inhibition of cell proliferation in an androgen-insensitive prostate cancer cell line (PC-3) transfected with a human androgen receptor complementary DNA. , 1993, Cancer research.

[30]  G. Prins,et al.  Regulation of proliferation and production of prostate-specific antigen in androgen-sensitive prostatic cancer cells, LNCaP, by dihydrotestosterone. , 1995, Endocrinology.

[31]  M. Rosser,et al.  Direct mitogenic effects of insulin, epidermal growth factor, glucocorticoid, cholera toxin, unknown pituitary factors and possibly prolactin, but not androgen, on normal rat prostate epithelial cells in serum-free, primary cell culture. , 1984, Cancer research.

[32]  J. Lechner,et al.  The Pasadena cell lines. , 1980, Progress in clinical and biological research.

[33]  A. Passaniti,et al.  Regulation of prostate‐specific antigen gene expression in LNCaP human prostatic carcinoma cells by growth, dihydrotestosterone, and extracellular matrix , 1994, The Prostate.

[34]  M. Blankenstein,et al.  Effect of culture conditions on androgen sensitivity of the human prostatic cancer cell line LNCaP , 1993, The Prostate.

[35]  A. Brinkmann,et al.  Mechanism of androgen action: recent observations on the domain structure of androgen receptors and the induction of EGF-receptors by androgens in prostate tumor cells. , 1989, Journal of steroid biochemistry.

[36]  M. Webber,et al.  Stepwise immortalization and transformation of adult human prostate epithelial cells by a combination of HPV-18 and v-Ki-ras. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[37]  L. Skoog,et al.  Immunohistochemistry and biochemistry in detection of androgen, progesterone, and estrogen receptors in benign and malignant human prostatic tissue , 1992, The Prostate.

[38]  H. Carter,et al.  Epidemiologic evidence regarding predisposing factors to prostate cancer , 1990, The Prostate.

[39]  P. Wingo,et al.  Cancer statistics, 1996 , 1996, CA: a cancer journal for clinicians.

[40]  O. Jänne,et al.  Androgen receptor and mechanism of androgen action. , 1993, Annals of medicine.

[41]  H. Wiley,et al.  Androgens regulate proliferation of human prostate cancer cells in culture by increasing transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF)/TGF-alpha receptor. , 1993, The Journal of clinical endocrinology and metabolism.

[42]  J. McNeal,et al.  Differential cytokeratin expression in normal, hyperplastic and malignant epithelial cells from human prostate. , 1990, The Journal of urology.

[43]  P. Weijerman,et al.  Characterization of adult human prostatic epithelial-cells immortalized by polybrene-induced DNA transfection with a plasmid containing an origin-defective sv40-genome. , 1994, International journal of oncology.