Expression and androgen regulation of C-CAM cell adhesion molecule isoforms in rat dorsal and ventral prostate

Makarovskiy, Andrew; Pu, Yeong-Shiau; Lo, Piao; Earley, Karen; Paglia, Michael J.; Hixson, Douglas C.; Lin, Sue-Hwa

doi:10.1038/sj.onc.1202665

Cited by 5 publications

(4 citation statements)

References 22 publications

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“…In the rat, the epithelial cells of every lobe are androgen-dependent but some genes, such as the one encoding for C-CAM epithelial celladhesion molecule, are distinctly regulated in the dorsal or lateral lobes with respect to the ventral ones after castration. 37 Thus, regulation by androgens of pro-AM gene expression or its alternative splicing may be different in the rat prostatic ventral lobe compared to the human prostate.…”

Section: Discussionmentioning

confidence: 99%

Peptidylglycine ?-amidating monooxygenase- and proadrenomedullin-derived peptide-associated neuroendocrine differentiation are induced by androgen deprivation in the neoplastic prostate

Jiménez¹,

Jongsma²,

Calvo³

et al. 2001

Int. J. Cancer

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Most PCs show NE differentiation. Several studies have tried to correlate NE expression with disease status, but the reported findings have been contradictory. Prostatic NE cells synthesize peptides with a wide spectrum of potential functions. Some of these active peptides, such as PAMP, are amidated. PAM is the only carboxy-terminal peptide-amidating enzyme identified. We studied expression of PAMP and PAM in normal prostate and prostatic tumors (clinical specimens and human xenograft models) with or without prior androgen-deprivation therapy and found a wide distribution of both molecules in NE subpopulations of all kinds. Although the correlation of either marker to tumor grade, clinical progression or disease prognosis did not reach statistical significance, PAMP-or PAM-immunoreactive cells were induced after androgen-blockade therapy. In the PC-310 and PC-295 androgen-dependent models, PAMP or PAM NE differentiation was induced after castration in different ways, being higher in PC-310, which might explain its long-term survival after androgen deprivation. We show induction of expression of 2 new NE markers in clinical specimens and xenografted PC after endocrine therapy.

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Section: Discussionmentioning

confidence: 99%

Peptidylglycine ?-amidating monooxygenase- and proadrenomedullin-derived peptide-associated neuroendocrine differentiation are induced by androgen deprivation in the neoplastic prostate

Jiménez¹,

Jongsma²,

Calvo³

et al. 2001

Int. J. Cancer

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“…Many protocols describing the long-term maintenance of rat prostate epithelial cultures require the pre-treatment of rats with carcinogens or testosterone prior to cell isolation or cell immortalization in primary culture using recombinant DNA methodologies. As an animal model for studying human prostatic cancer, the rat dorso-lateral region also more closely resembles human prostate than does the rat ventral lobe (Dunning, 1963; Makarovskiy et al, 1999). Furthermore, in terms of studying human prostatic cancer, the rat dorso-lateral region is prone to spontaneous and induced neoplasms and most closely resembles the outer or peripheral zone of the human prostate gland, a region that is most often associated with intraepithelial neoplasms (Makarovskiy et al, 1999; Valkenburg and Williams, 2011).…”

Section: Discussionmentioning

confidence: 99%

Soft agar-based selection of spontaneously transformed rat prostate epithelial cells with highly tumorigenic characteristics

Gajdošik

Hixson

Brilliant

et al. 2018

Experimental and Molecular Pathology

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The critical molecular and cellular mechanisms involved in the development and progression of prostate cancer remain elusive. In this report, we demonstrate that normal rat prostate epithelial cells (PEC) undergo spontaneous transformation at high passage (p > 85) evidenced by the acquisition of anchorage independent growth when plated on soft agar and tumorigenicity when injected into immunodeficient mice. In addition, we also report the discovery of a minor subpopulation of spontaneously transformed PEC derived from high passage PEC with the ability to migrate through a layer of 1% agar and form expanding colonies on the underlying plastic substratum. Comparison of these soft agar invasive (SAI) cells with low (p < 35), mid (p36-84) and high passage (p > 85) PEC identified marked differences in cell morphology, proliferation and motility. The SAI subpopulation was more tumorigenic than the high passage anchorage independent cultures from which they were isolated, as manifested by a decreased latency period and an increase in the size of tumors arising in immunodeficient mice. In contrast, low and mid passage cells were unable to grow on soft agar and failed to form tumors when injected into immunodeficient mice. Screening with antibody-based signaling arrays identified several differences in the altered expression levels of signaling proteins between SAI-derived cells and low or high passage PEC, including the up-regulation of EGFR and MAPK-related signaling pathways in SAI-selected cells. In summary, these studies suggest that the SAI assay selects for a novel, highly tumorigenic subpopulation of transformed cells that may represent an early step in the progression of slow growing prostatic carcinomas into more rapidly growing and aggressive tumors.

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“…Although all the rat lobes express androgen receptor, a distinct androgen regulation of certain proteins occurs in each particular type of lobe. For example, the expression of metalloproteases [48] or adhesion molecules, such as C‐CAM [49] is controlled by androgens in the rat ventral prostate, but not in the dorsal prostate. Therefore, the fact that AM expression is androgen‐dependent in the ventral lobes of the rat prostate does not imply a similar regulation in the dorsolateral lobes or in the human prostate.…”

Section: Discussionmentioning

confidence: 99%

Androgen‐independent expression of adrenomedullin and peptidylglycine α‐amidating monooxygenase in human prostatic carcinoma

Jiménez¹,

Abasolo²,

Jongsma³

et al. 2003

Molecular Carcinogenesis

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Most of the locally advanced and metastatic prostate carcinomas (PCs) treated with antiandrogenic therapy eventually become refractory to this treatment. Locally produced factors may control prostate tumor biology after androgen withdrawal. Adrenomedullin (AM) is expressed in the prostate and could control cell growth in androgen-independent conditions. AM needs to be amidated by the enzyme peptidylglycine alpha-amidating monooxygenase (PAM) to become fully active. The objective of the present study was to analyze whether the expression of preproadrenomedullin (preproAM) and PAM in PC is regulated by androgens. For this purpose, human in vitro and in vivo PC models were grown in the presence or absence of androgens, and the expression of AM and PAM was examined by immunohistochemistry, Western blotting, RT-PCR, and Northern blotting. Furthermore, immunohistochemical analysis of AM in clinical specimens was performed to test if its expression is related to Gleason score and antiandrogenic therapy. In PC cell lines and xenografts, mRNA and protein AM levels were similar in the presence or absence of androgens. PAM expression seemed to be induced by androgen-withdrawal. Our results in clinical samples showed no relationship between AM expression and Gleason score or antiandrogenic treatment. In conclusion, our results demonstrate that preproAM and PAM expression in the human prostate is androgen-independent. In addition, we also report for the first time the expression of a novel PAM transcript in PC, which has not been previously described in other tissues.

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Expression and androgen regulation of C-CAM cell adhesion molecule isoforms in rat dorsal and ventral prostate

Cited by 5 publications

References 22 publications

Peptidylglycine ?-amidating monooxygenase- and proadrenomedullin-derived peptide-associated neuroendocrine differentiation are induced by androgen deprivation in the neoplastic prostate

Peptidylglycine ?-amidating monooxygenase- and proadrenomedullin-derived peptide-associated neuroendocrine differentiation are induced by androgen deprivation in the neoplastic prostate

Soft agar-based selection of spontaneously transformed rat prostate epithelial cells with highly tumorigenic characteristics

Androgen‐independent expression of adrenomedullin and peptidylglycine α‐amidating monooxygenase in human prostatic carcinoma

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