Molecular mechanisms in hormone-resistant prostate cancer.
Prostate cancer is the most common malignancy in males. Despite the efforts for an early diagnosis, approximately one third of the cases are diagnosed in advanced clinical stages. Prostatic cancer, as the function of normal prostate is dependent upon androgens. So, androgenic deprivation represents an effective treatment especially in advanced cases. Although, the majority of patients will initially respond to androgen blockade, consequently the hormone-resistance will develop and the tumor will progress. The mechanism that determines tumoral progression during the endocrine treatment is driven by genomic instability, characterized by activating mutations of androgen receptor gene (AR), progression of some cellular clones possible of neuroendocrine origin that become adapted to low concentrations of residual adrenal androgens, suppression of apoptosis, by bcl-2 oncogene overexpression and p53 mutations, and growth factors (IGF-1--Insulin-like growth factor, KGF--keratinocyte growth factor, EGF--Epidermal growth factor, TGF a, b- Transforming growth factor a and b, bFGF--Fibroblastic growth factor type b) regulatory effect through either a paracrine or an autocrine mechanism. The identification of molecular alterations that appear during prostate carcinogenesis, may lead to the identification of new molecular targets to prevent hormone-resistance and to improve the prognosis in prostate cancers.
Roznovanu
Silvia Lăcrămioara
SL
CI Parhon Universitary Hospital Iaşi, Laboratory of Pathology, University of Medicine and Pharmacy Gr.T. Popa Iaşi, School of Medicine.
Amălinci
Cornelia
C
Rădulescu
Doiniţa
D
D000728:Androgens / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D019254:Genes, bcl-2; D016158:Genes, p53; D042822:Genomic Instability; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
C410798:AR protein, human; D000728:Androgens; D006133:Growth Substances; D011944:Receptors, Androgen; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D017526:Receptor, IGF Type 1