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Androgen receptor (AR) is a steroid hormone receptor that functions as a transcription factor for regulating cell growth and survival. Aberrant AR function becomes a risk factor for promoting the progression of prostate cancer (PCa). In this study, we examined the roles of proline-rich tyrosine kinase 2 (PYK2) and ribosomal S6 kinase 1 (S6K1) in regulating AR expression and activity and growth properties in PCa cells. Compared with normal prostate tissues, PCa tumors exhibited high levels of PYK2 and S6K1 expression. Furthermore, the expression levels of PYK2 and S6K1 were significantly correlated with nuclear AR expression in PCa tissues. We further found the association between PYK2, S6K1, and AR in their protein expression and phosphorylation levels among normal prostate PZ-HPV-7 cells and prostate cancer LNCaP and 22Rv1 cells. Overexpression of the wild-type PYK2 in PZ-HPV-7 and LNCaP cells promoted AR and S6K1 expression and phosphorylation as well as enhanced cell growth. In contrast, expression of the mutated PYK2 or knockdown of PYK2 expression in LNCaP or 22Rv1 cells caused reduced expression or phosphorylation of AR and S6K1 as well as retarded cell growth. Under an androgen-deprived condition, PYK2-promoted AR expression and phosphorylation and PSA production in LNCaP cells can be abolished by knocking down S6K1 expression. In summary, our data suggested that PYK2 via S6K1 activation modulated AR function and growth properties in PCa cells. Thus, PYK2 and S6K1 may potentially serve as therapeutic targets for PCa treatment.

This study considers both vertical and horizontal educational mismatches, with the former referring to overeducation and undereducation, and the latter to the mismatch between college major and job. It is found that the wage premium of the vertical educational match is greater than that of the horizontal educational match. A better vertical match augments the wage premium of an improvement in the horizontal match, and vice versa. The horizontal educational mismatch appears to be an extended scenario of overeducation because graduates from colleges with low rankings have a higher probability of being vertically overeducated as well as horizontally mismatched. Graduates from highly-ranked colleges are privileged to not only have high earnings but also to have low probabilities for the vertical and horizontal mismatches. These low probabilities indirectly raise their earnings. The indirect effects of academic characteristics on earnings are calculated. The approach we propose provides an insight into how academic characteristics comprehensively influence earnings.

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